Differential effects of ethanol on baroreceptor heart rate responses of conscious spontaneously hypertensive and normotensive rats

This study investigated the acute effects of ethanol (0.25, 0.5, or 1 g/kg, iv) on mean arterial pressure, heart rate, and gain of the baroreceptor reflex control of heart rate (BRS) in conscious spontaneously hypertensive rats (SHRs) and age-matched Wistar rats. BRS was substantially lower in the SHRs as compared with the Wistar rats when measured by phenylephrine (-0.95 +/- 0.16 vs. -2.02 +/- 0.22 beats/min/mm Hg) or nitroprusside (-1.90 +/- 0.2 vs -3.02 +/- 0.32 beats/min/mm Hg). None of the doses of ethanol influenced BRS in the SHR. In contrast, ethanol attenuated BRS in Wistar rats, but this effect was dependent on the dose used and the type of response. The lower doses attenuated the reflex tachycardic response, but had no effect on the reflex bradycardic response. On the other hand, the 1 g/kg dose of ethanol attenuated the reflex bradycardic but not the tachycardic response. Ethanol produced a pressor effect (15-25 mm Hg; 5-min duration), which was neither dose- nor strain-dependent. However, only in the SHR mean arterial pressure remained elevated (10-15 mm Hg above control) for 20 min in response to the 0.5 g/kg dose of ethanol, and its recovery coincided with the occurrence of a slowly developing negative chronotropic response. Ethanol produced a dose-related negative chronotropic effect in both strains of rats that was of longer duration in the SHR, particularly with the 1 g/kg dose. It is possible that the bradycardic effect of ethanol influenced negatively its pressor effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upregulation of imidazoline receptors in the medulla oblongata accounts for the enhanced hypotensive effect of clonidine in aortic barodenervated rats

The present study tested the hypothesis that an upregulation of the imidazoline receptor in the rostral ventrolateral medulla (RVLM) of aortic barodenervated (ABD) rats may account for the enhanced hypotensive effect of clonidine. In vitro autoradiographic radioligand binding studies were utilized to investigate the binding characteristics of imidazoline receptors in the RVLM and nucleus tractus solitarius (NTS), areas that play critical roles in cardiovascular regulation and elicitation of clonidine responses. ABD but not sham operation (SO) caused immediate and significant (P < 0.05) increases in mean arterial pressure (MAP) and heart rate (HR) and an impairment of the baroreflex-mediated HR response (baroreflex sensitivity, BRS). Two days after ABD, these parameters, except BRS, subsided to near-control (SO) levels. Intracisternal (i.c.) administration of clonidine (0.1 micrograms) elicited a 3-fold greater decrease in BP of conscious ABD compared with SO rats (-20.3 +/- 2.6 vs. -7.4 +/- 0.9 mmHg) thus demonstrating the ability of ABD to enhance centrally-mediated hypotensive responses. Autoradiographic visualization of brain sections obtained from separate groups of ABD and SO rats 48 h after surgery preincubated with [3H]idazoxan (2.5-3.5 nM) showed that [3H]idazoxan binding in RVLM, middle NTM (mNTS) and rostral NTS (rNTS) was saturable and of high affinity. Uneven distribution of imidazoline binding sites was evident since in control (SO) rats, Scatchard analysis of binding data revealed similar densities (Bmax) of [3H]idazoxan binding sites in the RVLM and mNTS versus significantly higher density in the rNTS. In ABD rats, the binding dissociation constant (Kd) was significantly decreased in both the RVLM (8.1 +/- 3.1 vs. 21.4 +/- 5.0 nM) and rNTS (12.3 +/- 1.3 vs. 18.6 +/- 3.1 nM) compared with SO rats while the Bmax was not affected. This finding suggests an increased receptor affinity in the RVLM and rNTS of barodenervated rats. The mNTS of ABD rats exhibited significant increases in the Bmax (861 +/- 96 vs. 570 +/- 87 fmol/mg protein) compared with values of SO rats but the receptor affinity was not affected. It is concluded that: (i) aortic baroreceptors exert a tonic inhibitory influence on central imidazoline receptor function; and (ii) the enhanced hypotensive effect of clonidine in conscious ABD rats may be accounted for by the increased affinity of the medullary imidazoline receptors particularly in the RVLM.     

ANP enhances bradycardic reflexes in normotensive but not spontaneously hypertensive rats

Baroreflex control of heart rate in spontaneously hypertensive rats (SHR) is defective, largely because of a poor vagal contribution to the reflex. We have demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia in normotensive rats through an action on nonarterial vagal afferent pathways. In the present study, we investigated whether ANP could reverse the baroreflex abnormality in SHR. Heart rate reflexes were activated by three different methods in conscious, instrumented SHR and Wistar-Kyoto rats (WKY) in the presence of intravenous infusions of vehicle (saline) or rat ANP (150 ng/kg per minute). Heart rate responses were measured by (1) the steady-state changes in blood pressure after alternating slow infusions (over approximately 15 to 30 seconds) of a pressor (methoxamine) and depressor (nitroprusside) drug (stimulating predominantly arterial baroreceptors), (2) the ramp method of rapid infusion of methoxamine (over < 10 seconds; stimulating arterial and cardiopulmonary baroreceptors), and (3) the von Bezold-Jarisch method of activating chemically sensitive cardiac receptors through serotonin injections. ANP enhanced the heart rate range of the arterial baroreflex (steady-state method) by 13 +/- 3% in WKY but had no significant effect on the sensitivity or any other parameter of the steady-state baroreflex. When a very rapid rise in blood pressure was elicited by the ramp method in WKY, ANP significantly enhanced baroreflex bradycardia (sensitivity increased by 29 +/- 9%, P < .05). ANP also enhanced the bradycardia of the von Bezold-Jarisch reflex (by 33 +/- 16%, P < .05) in WKY. By contrast, ANP did not influence baroreceptor or chemoreceptor heart rate reflex responses in SHR. We conclude that in normotensive rats, ANP facilitates cardiopulmonary bradycardic reflexes. The lack of effect of ANP in SHR may be related to an underlying structural or genetic alteration in their cardiac sensors, perhaps associated with cardiac hypertrophy, that prevents the ANP-induced activation of cardiac sensory afferents, resulting in cardioinhibition.     

Effects of sinoaortic denervation on Fos expression in the brain evoked by hypertension and hypotension in conscious rabbits

We have previously shown [Li and Dampney (1994) Neuroscience 61, 613-634] that periods of sustained hypertension and hypotension each induces a distinctive and reproducible pattern of neuronal expression of Fos (a marker of neuronal activation) in specific regions of the brainstem and forebrain of conscious rabbits. The aim of this study was to determine the contribution of afferent inputs from arterial baroreceptors to the activation of neurons in these various brain regions that is caused by a sustained change in arterial pressure. Experiments were carried out on rabbits in which the carotid sinus and aortic depressor nerves were cut in a preliminary operation. Following a recovery period of seven to 10 days, a moderate hypertension or hypotension (increase or decrease in arterial pressure of 20-30 mmHg) was induced in conscious barodenervated rabbits for 60 min by the continuous infusion of phenylephrine or sodium nitroprusside, respectively. In control experiments, barodenervated rabbits were subjected to the identical procedures except that they were infused with the vehicle solution alone. Compared with the effects seen in barointact rabbits, [Li and Dampney (1994) Neuroscience 61, 613-634] the number of neurons that expressed Fos in response to hypertension was reduced by approximately 90% in the nucleus of the solitary tract and in the caudal and intermediate parts of the ventrolateral medulla. In supramedullary regions, baroreceptor denervation resulted in a reduction of approximately 60% in hypertension-induced Fos expression in the central nucleus of the amygdala and in the bed nucleus of the stria terminalis, but no significant reduction in the parabrachial complex in the pons. Following hypotension, the number of neurons that expressed Fos in barodenervated rabbits, compared with barointact rabbits, [Li and Dampney (1994) Neuroscience 61, 613-634] was reduced by approximately 90% in the nucleus of the solitary tract, area postrema, and caudal, intermediate and rostral parts of the ventrolateral medulla. Baroreceptor denervation also resulted in a similar large reduction in hypotension-induced Fos expression in many supramedullary regions (locus coeruleus, midbrain periaqueductal grey, hypothalamic paraventricular nucleus, and in the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the basal forebrain). In the supraoptic nucleus, hypotension-induced Fos expression in barodenervated rabbits was reduced by 75% compared to barointact animals, but was still significantly greater than in control animals. There was also a high level of Fos expression, much greater than in control animals, in the circumventricular organs surrounding the third ventricle (subfornical organ and organum vasculosum lamina terminalis). The results indicate that in conscious rabbits the activation of neurons that occurs in several discrete regions at all levels of the brain following a sustained change in arterial pressure is largely dependent upon inputs from arterial baroreceptors, with the exception of neurons in the circumventricular organs surrounding the third ventricle that are activated by sustained hypotension. The latter group of neurons are known to project to vasopressin-secreting neurons in the supraoptic nucleus, and may therefore via this pathway trigger the hypotension-induced release of vasopressin that occurs in the absence of baroreceptor inputs.     

Desflurane-mediated sympathetic activation occurs in humans despite preventing hypotension and baroreceptor unloading

BACKGROUND: Increasing concentrations of desflurane result in progressive decreases in blood pressure (BP) and, unlike other currently marketed, potent volatile anesthetics, heightened sympathetic nervous system activity. This study aimed to determine whether baroreflex mechanisms are involved in desflurane-mediated sympathetic excitation. METHODS: Healthy volunteers were anesthetized with desflurane (n = 8) or isoflurane (n = 9). Heart rate (HR; measured by electrocardiograph), blood pressure (BP; measured by arterial catheter), and efferent sympathetic nerve activity (SNA; obtained from percutaneous recordings from the peroneal nerve) were monitored. Baroreflex sensitivity was evaluated at baseline while volunteers were conscious and during 0.5, 1, and 1.5 minimum alveolar concentration (MAC) anesthesia via bolus injections of nitroprusside (100 microg) and phenylephrine (150 microg) to decrease and increase BP. To prevent the BP decline with increasing depths of anesthesia, phenylephrine was infused to maintain mean BP at the 0.5 MAC level. RESULTS: The HR, BP, and SNA were similar between the groups at the conscious baseline measurement. Efferent SNA did not change during higher MAC of isoflurane, but it increased progressively as desflurane concentrations were increased beyond 0.5 MAC, despite maintaining BP at the 0.5 MAC value with phenylephrine infusions (P < 0.05). Cardiac baroslopes (based on changes in HR) were progressively and similarly decreased with increasing concentrations of isoflurane and desflurane (P < 0.05). Sympathetic baroslopes (based on SNA) decreased with increasing isoflurane concentrations but were maintained with increasing concentrations of desflurane; the response was significantly different between groups. CONCLUSIONS: The increase in basal levels of SNA with increasing concentrations of desflurane persisted despite "fixing" BP and thus is probably not due to hypotension and unloading of the baroreceptors. Further, the preservation of reflex increases in SNA to nitroprusside during desflurane indicates that desflurane preserves one component of the baroreflex in humans when BP is "fixed."     

Decreased cardiac baroreflex sensitivity is not due to cardiac hypertrophy in NG-nitro-L-arginine methyl ester-induced hypertension

OBJECTIVE: To investigate the link between cardiac hypertrophy, elevated blood pressure level and baroreflex impairment, we assessed cardiac baroreflex function in a hypertensive model almost devoid of cardiac hypertrophy, obtained by nitric oxide synthesis inhibition. METHODS: Thirteen adult male Wistar rats were treated orally with NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg per 24 h) for 4 weeks. Fifteen control rats received tap water. At the end of the treatment aortic blood pressure was recorded continuously and the baroreceptor-heart rate curve was assessed by bolus injections of phenylephrine and sodium nitroprusside (10 different doses of each). RESULTS: Mean blood pressure was higher in L-NAME rats than in control rats, whereas body weight was similar. Total heart weight and left ventricular weight did not differ between the groups. Cardiac baroreflex was reset in hypertensive rats, as indicated by a rightwards shift of the mean blood pressure-heart rate curve. Its gain was decreased significantly in L-NAME rats, whereas the heart rate range was not different between the two groups. CONCLUSION: L-NAME hypertensive rats exhibit an original impairment of cardiac baroreflex, characterized by a range-independent decreased gain which is not due to cardiac hypertrophy.     

Antihypertensive effects of food-intake restriction in aortic coarctation hypertension

OBJECTIVE: To test the hypothesis that reductions in mean arterial pressure (MAP) induced by food-intake restriction in aortic coarctation hypertension are the result of a reduction of the sympathetic support of the MAP. We also wanted to determine whether the baroreflex control of the heart rate, and alpha- and beta-adrenergic responsivenesses were influenced by chronic food-intake restriction. METHODS: Four days after aortic coarctation, female Sprague-Dawley rats were assigned to a group that had access ad libitum to food (CON; n = 19) or to a food-intake-restricted group (FRG; n = 17) that was allowed 60% of the CON group's food intake per rat. After 3 weeks, carotid and jugular catheters were implanted for measurement of the MAP and infusion of drugs into conscious rats. The sympathetic contribution to the blood pressure was assessed by measuring the depressor response to ganglionic blockade by hexamethonium plus atropine (30.0 and 0.1 mg/kg intravenously). The baroreflex control of the heart rate was assessed by administering alternating bolus doses of phenylephrine and nitroprusside. The alpha-adrenergic sensitivity was assessed by measuring the response of the MAP to phenylephrine in areflexive rats (after ganglionic blockade), and the beta-adrenergic sensitivity was assessed by measuring the responses of the MAP and heart rate to isoproterenol administration both in reflexive and in areflexive rats. RESULTS: Four days after catheterization, both the MAP (CON 150 +/- 5 mmHg, FRG 116 +/- 4 mmHg) and the heart rate (CON 414 +/- 8 beats/min, FRG 365 +/- 11 beats/min) were significantly lower in rats of the FRG. That the sympathetic support of the MAP had diminished in FRG rats was evidenced by an attenuated depressor response to ganglionic blockade (40 +/- 3 versus 65 +/- 3 mmHg). FRG rats exhibited significantly greater reflex bradycardia in response to phenylephrine (slope -1.44+/- 0.07 versus -0.54 +/- 0.05 beats/min per mmHg), whereas their reflex tachycardia was not altered (slope -1.58 +/- 0.08 versus -1.53 +/- 0.13 beats/min per mmHg). FRG rats also displayed blunted responses of the heart rate and MAP to isoproterenol administration. CONCLUSION: Food-intake restriction attenuates the rise in MAP which occurs after aortic coarctation significantly. The antihypertensive effect of food-intake restriction may be mediated via a reduction in sympathetic tone.     

Characterization of endothelium-dependent vasodilation and vasoconstriction in coronary arteries from spontaneously hypertensive rats

Coronary artery disease often occurs in patients with hypertension. The present study was designed to evaluate coronary vascular function in isolated coronary arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats and to determine the effect of antihypertensive treatment on coronary vascular responsiveness. Male SHR and WKY rats (12 to 14 weeks old) were divided into control and hydralazine-treated (120 mg/L drinking water for 10 days) groups. After 10 days, arterial pressure and heart rate were recorded while rats were conscious and unrestrained. Left ventricular coronary arteries (200 to 300 microns diameter) were isolated and intraluminal diameter was continuously recorded while vessels were maintained at a constant intraluminal pressure of 40 mm Hg. Relaxation of coronary arteries to both acetylcholine and nitroprusside was slightly, but significantly, enhanced in vessels from SHR compared to WKY rats. The enhanced relaxation was a specific effect, since isoproterenol induced similar relaxation in coronary arteries from SHR and WKY rats. Contraction to phenylephrine, but not endothelin-1, was augmented in coronary arteries from SHR compared to WKY rats. Treatment with hydralazine significantly lowered arterial pressure in SHR and WKY rats, but did not alter the enhanced contraction to phenylephrine or the enhanced relaxation to acetylcholine and nitroprusside in coronary arteris from SHR. These results indicate that coronary arteries of 12 to 14 week-old SHR do not have impaired endothelium-dependent relaxation, but to exhibit enhanced alpha-adrenoceptor-mediated contraction that is not reduced by lowering arterial pressure.     

Sigmoidal curve-fitting of baroreceptor sensitivity in renovascular 2K1C hypertensive rats

The time course of changes in baroreceptor reflex sensitivity in Goldblatt two-kidney one clip (2K1C) hypertension was studied 3, 7 and 30 days after renal artery clipping by means of a sigmoidal curve-fitting analysis. Experiments were performed in 54 adult male Wistar rats (N = 9 per group) weighing 200-300 g. The reflex heart rate responses were elicited by alternate intravenous bolus injections of phenylephrine (delta +5 to +50 mmHg) and sodium nitroprusside (delta -5 to -50 mmHg). A clear upper and lower plateau (reflex tachycardia and bradycardia, respectively) was noted in both sham and hypertensive groups. Although the resting mean arterial pressure was significantly increased in all hypertensive groups (131 +/- 3, 149 +/- 7 and 168 +/- 11 mmHg, respectively, 3, 7 and 30 days after clipping), when compared to the sham group (108 +/- 2 mmHg), significant changes in baroreceptor reflex function were observed only in 7- and 30-day groups. Baroreflex sensitivity was markedly reduced in these hypertensive rats (2.3 +/- 0.3 and 1.9 +/- 0.3 bpm/mmHg, respectively) compared to the sham group (4.2 +/- 0.3 bpm/mmHg). In addition, a reduced baroreflex heart rate range was observed in these groups (117 +/- 12 and 107 +/- 10 bpm, respectively) compared to the sham group (165 +/- 11 bpm). These data indicate an impairment of baroreflex function in conscious 2K1C hypertensive rats which seems to be secondary to arterial hypertension.     

Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid hemorrhage

The hemodynamic responses to acute (45 min) partial aortic constriction were studied in conscious intact (N = 7) or sinoaortic denervated (SAD) adult male Wistar rats (280-350 g, N = 7) implanted with carotid and femoral arterial catheters, a pneumatic cuff around the abdominal aorta and a pulsed Doppler flow probe to measure changes in aortic resistance. In addition, the hypertensive response and the reflex bradycardia elicited by total (N = 8) vs partial (N = 7) aortic constriction (monitored by maintenance of the pressure distal to the cuff at 50 mmHg) were compared in two other groups of intact rats. Intact rats presented a smaller hypertensive response (26 to 40% above basal level) to partial aortic constriction than SAD rats (38 to 58%). The calculated change in aortic resistance imposed by constriction of the aorta increased progressively only in intact rats, but was significantly smaller (193 to 306%) than that observed (501 to 591%) in SAD rats. Intact rats showed a significant bradycardia (23 to 26% change in basal heart rate) throughout coarctation, whereas the SAD rats did not (1 to 3%). Partial or total occlusion of the aorta induced similar hypertensive responses (37-38% vs 24-30% for total constriction) as well as reflex bradycardia (-15 to -17% vs -22 to -33%) despite a greater gradient in pressure (97-98 vs 129-140 mmHg) caused by total constriction. The present data indicate that the integrity of the baroreflex in intact rats can cause the hypertensive response to level off at a lower value than in SAD rats despite a progressive increase in aortic resistance. In addition, they also indicate that the degree of partial aortic constriction by maintenance of the pressure distal to the cuff at 50 mmHg already elicits a maximal stimulation of the arterial baroreflex.     

Effects of sodium nitroprusside and phenylephrine on blood flow in free musculocutaneous flaps during general anesthesia

BACKGROUND: Hypoperfusion and necrosis in free flaps used to correct tissue defects remain important clinical problems. The authors studied the effects of two vasoactive drugs, sodium nitroprusside and phenylephrine, which are used frequently in anesthetic practice, on total blood flow and microcirculatory flow in free musculocutaneous flaps during general anesthesia. METHODS: In a porcine model (n = 9) in which clinical conditions for anesthesia and microvascular surgery were simulated, latissimus dorsi free flaps were transferred to the lower extremity. Total blood flow in the flaps was measured using ultrasound flowmetry and microcirculatory flow was measured using laser Doppler flowmetry. The effects of sodium nitroprusside and phenylephrine were studied during local infusion through the feeding artery of the flap and during systemic administration. RESULTS: Systemic sodium nitroprusside caused a 30% decrease in mean arterial pressure, but cardiac output did not change. The total flow in the flap decreased by 40% (P < 0.01), and microcirculatory flow decreased by 23% in the skin (P < 0.01) and by 30% in the muscle (P < 0.01) of the flap. Sodium nitroprusside infused locally into the flap artery increased the total flap flow by 20% (P < 0.01). Systemic phenylephrine caused a 30% increase in mean arterial pressure, whereas heart rate, cardiac output, and flap blood flow did not change. Local phenylephrine caused a 30% decrease (P < 0.01) in the total flap flow. CONCLUSIONS: Systemic phenylephrine in a dose increasing the systemic vascular resistance and arterial pressure by 30% appears to have no adverse effects on blood flow in free musculocutaneous flaps. Sodium nitroprusside, however, in a dose causing a 30% decrease in systemic vascular resistance and arterial pressure, causes a severe reduction in free flap blood flow despite maintaining cardiac output.     

Cardiovascular responses to cholinergic agonists in sinoaortic denervated rats

1. The cardiovascular effect of systemic nicotinic and muscarinic cholinergic stimulation were studied in conscious sham operated and sinoaortic denervated (SAD) rats, 7 days after the corresponding operation. 2. The administration of the nicotinic ganglionic agent, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 50-100 micrograms.kg-1, i.v.) induced a fall of heart rate that was significantly higher in SAD rats than in sham rats. DMPP induced in sham rats an increase of arterial pressure but in SAD animals a biphasic response: an initial hypotension followed by an increase of arterial pressure. 3. Under muscarinic blockade, DMPP only showed a pressor and tachycardic action in both groups of rats without differences between them. 4. The muscarinic agonist, carbachol (0.1-10 micrograms.kg-1, i.v.) showed the same hypotensive and bradycardic action in both groups of rats. 5. Our results suggest that after 7 days of SAD, differences in the response to DMPP between sham and denervated animals could be due to the loss of baroreflex mechanisms. The increased bradycardic effect of DMPP in SAD rats could be mediated by a supersensitivity of parasympathetic ganglionic nicotinic receptors, whilst the sympathetic ganglionic nicotinic receptors remained unaltered. On the other side, the cardiovascular muscarinic responses to carbachol remain unaffected in SAD rats.     

Decreased baroreflex sensitivity in patients with stable coronary artery disease is correlated with the severity of coronary narrowing

Although studies have shown that arterial baroreflex sensitivity (BRS) is decreased in patients with acute myocardial infarction, BRS changes in patients with stable coronary artery disease (CAD) have not been studied extensively. We assessed BRS by the phenylephrine method in 55 normotensive and nondiabetic patients with chronic effort angina, old myocardial infarction, or both. The control group consisted of 24 age-matched patients without coronary lesions. To identify factors that determine BRS in stable CAD, we performed multivariate analysis using age, sex, left ventricular ejection fraction, pulmonary artery wedge pressure, resting systolic blood pressure, resting heart rate, the number of stenotic coronary arteries, history of myocardial infarction, and the presence or absence of angina pectoris as variables. BRS was significantly lower in patients with CAD than in control subjects (5.9 +/- 2.9 vs 6.9 +/- 2.4 ms/mm Hg, p < 0.05). In patients with CAD, BRS was inversely correlated with age, the resting heart rate, and the number of stenotic coronary vessels (p < 0.001, p < 0.005, and p < 0.005, respectively), but was independent of other clinical parameters, including the history of myocardial infarction. In control subjects, BRS was significantly correlated only with age. These results indicate that BRS is decreased in patients with stable CAD, and this decrease is correlated with the extent and severity of coronary narrowing.     

Effects of hypovolemia on aortic baroreflex control of heart rate in humans

INTRODUCTION: To test the hypothesis that hypovolemia can acutely increase the sensitivity of chronotropic baroreflex response, eight men (21-45 yr old) underwent measurements of heart rate response to aortic baroreceptor stimulation under normovolemic and hypovolemic conditions. METHODS: Hypovolemia was acutely induced by a bolus injection of 30 mg of furosemide. The sensitivity of the aortic-cardiac baroreflex was determined with a approximately 15 mmHg elevation in mean arterial pressure (MAP) induced by steady-state infusion of 30 to 97 micrograms.min-1 phenylephrine (PE) combined with approximately 13 mmHg lower body negative pressure (LBNP) to counteract central venous pressure elevations, and 17-19 mmHg neck pressure (NP) to offset increases in carotid sinus transmural pressure. The aortic-cardiac baroreflex gain was assessed by determining the ratio of the change in heart rate to the change in MAP (delta HR/delta MAP) between baseline and aortic baroreceptor isolated conditions (i.e., PE + LBNP + NP stage). RESULTS: When compared to normovolemia (3182 +/- 163 ml), furosemide-induced hypovolemia (2812 +/- 101 ml) resulted in an average 12% reduction in plasma volume (p = 0.05). Hypovolemia increased the average gain of the aortic-cardiac baroreflex by 68% (0.71 +/- 0.26 to 1.19 +/- 0.37 beats.min-1.mmHg-1; p = 0.0349) while it had no effect on the calculated response of the carotid-cardiac baroreflex. CONCLUSIONS: These results indicate that greater aortic baroreflex sensitivity observed in individuals who are physically untrained or have been exposed to microgravity may be explained by smaller vascular volume rather than differences in autonomic function associated with adaptations to lower aerobic capacity.     

Endurance training, overtraining and baroreflex sensitivity in female athletes

We examined heavy training-induced changes in baroreflex sensitivity, plasma volume and resting heart rate and blood pressure variability in female endurance athletes. Nine athletes (experimental training group, ETG) increased intense training (70-90% VO2max) volume by 130% and low-intensity training (< 70% Vo2max) volume by 100% during 6-9 weeks, whereas the corresponding increases in six control athletes (CG) were 5% and 10% respectively. Maximal oxygen uptake (VO2max) in the ETG and CG did not change, but in five ETG athletes VO2max decreased from 53.0 +/- 2.2 (mean +/- SEM) (CI 46.8-59.2) ml kg-1 min-1 to 50.2 +/- 2.3 (43.8-56.6) ml kg-1 min-1 (P < 0.01), indicating overtraining. Baroreflex sensitivity (BRS) measured using the phenylephrine technique and blood pressure variability (BPV) did not change, but the low-frequency power of the R-R interval variability increased in the ETG (P < 0.05). The relative change in plasma volume was 7% in the ETG and 3% in the CG. The changes in BRS did not correlate with the changes in plasma volume, heart rate variability and BPV. We conclude that heavy endurance training and overtraining did not change baroreflex sensitivity or BPV but significantly increased the low-frequency power of the R-R interval variability during supine rest in female athletes as a marker of increased cardiac sympathetic modulation.     

Effect of inhibition of nitric oxide synthesis on the uptake of LDL and fibrinogen by arterial walls and other organs of the rat

1. The effects of administering 3 mg ml-1 NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO), on the uptake of low density lipoprotein (LDL), fibrinogen and blood pressure were determined in conscious, unrestrained, cannulated normotensive and spontaneously hypertensive (SHR) Wistar rats. 2. The uptake of LDL and fibrinogen, labelled respectively with 125I or 131I via the adduct tyramine cellobiose ([125I]TC-LDL and [131I]TC-fibrinogen), were compared in aortic walls, heart, skeletal muscle, lung, liver, kidney and adrenal during the final 24 h of 6 days' administration of L-NAME in the drinking water. 3. In control normotensive rats, the systolic blood pressure did not change significantly over 6 days, while administration of L-NAME in normotensive rats increased the blood pressure progressively and significantly to about 170 mmHg over the same period. 4. In normotensive rats L-NAME increased significantly the uptake of both LDL and fibrinogen by aortic walls and heart, but not by muscle, lung, liver, kidney and adrenal. 5. The blood pressure in SHR was about 170 mmHg before administration of L-NAME and did not increase significantly after 6 days of treatment. In these rats the uptake of LDL or of fibrinogen was increased only in the heart but not in aortic walls nor in any of the other organs. 6. In normotensive rats the increase in blood pressure caused by inhibition of NO generation was associated with increases in the uptake of the atherogenic plasma proteins LDL and fibrinogen by the wall of the aorta and by the heart but not by the skeletal muscle, lung, liver, kidney and adrenal. The slightly higher blood pressure of SHR treated with L-NAME was not associated with increased uptake of LDL or fibrinogen by aorta nor by any organ except heart. Thus, while in normotensive rats the increase in blood pressure caused by inhibition of NO generation was associated with increase in the uptake of atherogenic plasma proteins LDL and fibrinogen by the wall of the aorta and by the heart, in SHR which showed uptakes similar to the normotensive animals, the non-significant increase in blood pressure induced by inhibition of NO generation was not associated with increased uptake of LDL or fibrinogen in any organ except the heart.7. These results are consistent with effects, demonstrated earlier, of infusing the pressor agents noradrenaline, adrenaline and angiotensin II, which produce increases in uptake of LDL and fibrinogen by aortic wall, whereas this is not so in spontaneously hypertensive rats.     

Progesterone-dependent decidualization of the human endometrium is mediated by cAMP

BACKGROUND: Behavioral stress has been proposed to contribute to the occurrence of myocardial ischemia. Objective To investigate the effect of chronic exposure to behavioral stress on the function and structure of the coronary artery of borderline hypertensive rats (BHR). DESIGN: BHR were either exposed to an air-jet stress for 2 h/day for 10 days or kept in their cage for 10 days. METHODS: After 10 days, hemodynamic measurements in conscious animals were recorded, and their hearts were removed for isolation of a left ventricular coronary artery for functional studies or for fixation by retrograde perfusion for study with scanning electron microscopy. Vascular reactivity was measured in isolated coronary arteries (approximately 250 microm) maintained at an intraluminal diameter of 40 mmHg while the intraluminal diameter was recorded continuously. RESULTS: The resting mean arterial pressure and heart rate in conscious, unrestrained BHR were not altered significantly by exposure to 10 days of 2 h/day air-jet stress. Coronary artery relaxation in response to the endothelium-dependent vasodilator acetylcholine was impaired in rats exposed to the air-jet stress compared with that in controls. An attenuated response to exogenous nitric oxide in coronary arteries from stressed BHR was confirmed by the finding of a reduced sensitivity to nitroprusside, which releases nitric oxide independently from the endothelium. However, relaxation of coronary arteries in response to isoproterenol, which acts independently from nitric oxide, was not altered. Coronary artery contraction in response to endothelin-1 and phenylephrine was not altered in vessels taken from BHR exposed to behavioral stress compared with that in vessels from control rats. Scanning electron microscopy of the endothelial surface of the septal coronary artery showed no difference between vessels from control and stressed BHR. CONCLUSION: These results indicate that behavioral stress impairs endothelium-dependent and nitric oxide-mediated coronary relaxation, but does not alter alpha1-adrenoceptor or endothelin-1-mediated contraction. By impairing coronary artery vascular relaxation, chronic exposure to behavioral stress may contribute to myocardial ischemia.     

Cardiovascular and sympathetic effects of proadrenomedullin NH2-terminal 20 peptide in conscious rats

Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin (AM), which are derived from the same gene, are novel vasodilative peptides and have been shown to exhibit hypotensive action in anesthetized animals. To avoid the modification via anesthesia, we investigated the effects of intravenously administered PAMP on mean arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) relative to those of AM in conscious unrestrained rats. We also examined whether the arterial baroreceptor reflex was altered with the two peptides. Intravenous injection of rat PAMP (rPAMP) (10, 20 and 50 nmol/kg) and rat AM (rAM) (0.3, 1.0 and 3.0 nmol/kg) similarly elicited dose-related hypotension accompanied by increases in HR and RSNA. However, the responses to rPAMP were less potent in magnitude and shorter in duration than those to rAM. Moreover, rAM facilitated baroreflex control, whereas rPAMP attenuated it. These findings indicate that although PAMP, as well as AM, may play an important role as a circulating hormone in the systemic circulation of conscious rats, the two peptides derived from an identical origin might have different mechanisms responsible for their cardiovascular and RSNA actions.     

Relationship between mechanical properties of the carotid artery wall and baroreflex function in acutely treated hypertensive patients

OBJECTIVE: To evaluate the relationship between the mechanical properties of the carotid artery wall and baroreflex function after acute reduction of blood pressure with lacidipine in essential hypertension. DESIGN: After 15 days of placebo washout, the hypertensive patients underwent a single-blind haemodynamic study before and 90 min after administration of 4 mg lacidipine (a dihydropyridine calcium antagonist). METHODS: Brachial intra-arterial blood pressure was recorded in eight mild-to-moderate essential hypertensive patients aged 40-53 years (mean +/- SEM 46.8 +/- 4.7 years). The carotid pulse diameter was recorded simultaneously by an echo-tracking technique. The mechanical properties of the carotid artery wall were evaluated by calculating Peterson's incremental elastic modulus (Ep) both as an averaged value of 10 heart cycles with stable blood pressure and was the dynamic correlation, on a beat-to-beat basis, of Ep and the systolic blood pressure during a 20 mmHg increase in blood pressure following a bolus injection of phenylephrine. The elastic properties of the carotid artery were investigated further by determining the correlation between the systolic pressure and systolic diameter, beat by beat, during a ramped increase of blood pressure after phenylephrine administration. The baroreceptor reflex sensitivity was measured simultaneously by the Oxford method and by correlating Ep and the electrocardiographic R-R' interval on a beat-to-beat basis during phenylephrine injections. RESULTS: After lacidipine administration Peterson's elastic modulus, measured under resting steady-state conditions, was reduced (18.7 +/- 7.4 versus 16.4 +/- 6 x 10(5) dyne/cm2), whereas the baroreflex sensitivity was unchanged (6.6 +/- 3.3 versus 6.3 +/- 0.2 ms/mmHg) and resetting of the baroreflex had occurred. At the same time, the correlations between the systolic blood pressure and Ep and between the systolic blood pressure and carotid systolic diameter over a 20 mmHg increase in blood pressure were unchanged. Moreover, the correlations between the systolic blood pressure and the R-R' interval and between Ep and R-R' interval during the phenylephrine-induced blood pressure increase did not differ statistically. CONCLUSIONS: The results suggest that the resetting of the baroreflex after the acute reduction in blood pressure caused by lacidipine is dissociated from mechanical changes in the carotid artery wall.     

Relative contributions of cardiopulmonary and sinoaortic baroreflexes in causing sympathetic activation in the human skeletal muscle circulation during orthostatic stress

The aim of this study was to reexamine the hypothesis that cardiopulmonary baroreflexes are more important than sinoaortic baroreflexes in causing vasoconstriction in the skeletal muscle circulation during orthostatic stress. We recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve (and forearm blood flow with venous occlusion plethysmography) in normal subjects (innervated ventricles) and in heart transplant recipients (denervated ventricles) during graded lower body negative pressure (LBNP) performed alone and in combination with intravenous infusion of phenylephrine, which was titrated to eliminate the orthostatically induced fall in blood pressure and thus the unloading of both carotid and aortic baroreceptors. The principal new findings are as follows: (1) The increases in both MSNA and forearm vascular resistance during multiple levels of LBNP were not attenuated by heart transplantation, which causes ventricular but not sinoaortic deafferentation. (2) In heart transplant recipients, a small increase in MSNA during mild LBNP was dependent on a decrease in arterial pressure, but in normal subjects, a similar increase in MSNA occurred in the absence of any detectable decrease in the aortic pressure stimulus to the sinoaortic baroreceptors. (3) In normal subjects, the large increase in MSNA during a high level of LBNP was dependent on a decrease in arterial pressure and could be dissociated from the decrease in central venous pressure. Taken together, the findings strongly suggest that sinoaortic baroreflexes are much more important and ventricular baroreflexes are much less important than previously thought in causing reflex sympathetic activation and vasoconstriction in the human skeletal muscle circulation during orthostatic stress.