Role of spinal alpha adrenoceptor in the inhibition of renal sympathetic nerve activity and natriuresis induced by blood volume expansion in rabbits

The effect of spinal alpha adrenoceptor blockage on the inhibition of renal sympathetic nerve activity (RSNA) and natriuresis induced by blood volume expansion was investigated in anesthetized and bilateral sinoaortic denervated rabbits. In the groups of rabbits with intrathecal injection of alpha-adrenoceptor blocker phentolamine or artificial cerebrospinal fluid the inhibition of RSNA induced by blood volume expansion were (-25.4 +/- 5.4)% and (-42.5 +/- 5.2)% respectively (P < 0.05). In the groups of rabbits with intrathecal injection of alpha 1 adtenoceptor blocker prazosin or artificial cerebrospinal fluid the inhibition of RSNA induced by blood volume expansion were (-29.3 +/- 6.1)% and (-42.5 +/- 5.2)% respectively (P < 0.05). These results suggested that both spinal alpha and alpha 1 adrenceptor blockage with attenuated the inhibition of RSNA induced by blood volume expansion. The spinal alpha 1 adrenceptor blockage with intrathecal injection of prazosin also attenuated signiticantly the natriuresis and diuresis induced by blood volume expansion (P < 0.05).     

Epidural midazolam attenuates renal sympathetic nerve activity in rabbits

The effects of epidural midazolam on heart rate (HR), mean arterial pressure (MAP) and the renal sympathetic nerve activity (RSNA) were examined. Under alpha-choloralose anesthesia, 31 male Japanese-white rabbits received epidural catheterization and surgical procedures for measurement of the renal sympathetic nerve activity. Epidural low (0.05%) and high (0.5%) concentrations of midazolam did not affect HR, but significantly decreased MAP and RSNA-spikes (the spike count of RSNA). Intravenous flumazenil significantly increased MAP and RSNA-spikes. These findings suggest that the decrease in RSNA-spikes induced by epidural midazolam is derived from the benzodiazepine receptor. Intramuscular midazolam (0.5%) did not affect HR, but decreased MAP and RSNA-spikes significantly. In the spinal cord dissected rabbits, epidural midazolam (0.5%) did not affect HR and MAP, but significantly attenuated RSNA-spikes. In conclusion, epidural midazolam attenuated RSNA through the benzodiazepine receptors of both the spinal and supraspinal nervous system.     

Medullary mechanism of the inhibition on renal sympathetic efferent activities by stimulation of the cervical vagal afferent nerve in rabbits

The presence of angiographic evidence of thrombus is generally thought to be a contraindication to coronary stent placement. This report describes four patients in whom angiographic thrombus was lysed using the Dispatch infusion catheter prior to coronary stenting. Urokinase was infused via the Dispatch catheter with resolution of angiographic evidence of thrombus in all cases. No complications were encountered using this technique, and all patients had excellent angiographic results after stenting. We conclude that lysis of intracoronary thrombus using the Dispatch infusion catheter is feasible and appears safe in this small study. Further trials are needed to determine if this technique reduces the acute stent thrombosis rate compared to other techniques for stent deployment in the presence of angiographic evidence of thrombus.     

Facilitation of adrenal sympathetic efferent nerve activity induced by mechanical stimulation of teeth in the rat

The effects of afferent signals from the periodontal mechanoreceptors and muscle spindles of jaw-closing muscles on adrenal nerve activity were examined using anesthetized rats. The adrenal nerve activity increased with pressure stimulation of the teeth and by biting a wooden stick. However, after denervation of the periodontal ligament, the facilitation due to the stick-biting was not observed. These results indicate that periodontal afferents facilitate adrenal nerve activity.     

Evaluation by microneurography of muscle sympathetic nerve activity in myelopathic patients

The purpose of this study was to observe the functional condition of the muscle sympathetic nerve activity (MSNA) in nine patients with mild myelopathy for which surgery was indicated [mean score 14/17 by Japanese Orthopaedic Association (JOA) cervical myelopathy and 7/11 for thoracic myelopathy]. The MSNA was obtained from the tibial nerve at the popliteal fossa by microneurography. The resting activities and the responses during handgripping were analyzed and compared with those of a control group of nine healthy volunteers and patients with disorders unrelated to myelopathy. The MSNA with the subjects supine was recorded first at rest for 5 min. (rest period), next during exertion of 20% of the maximum voluntary handgripping power for 5 min. (handgripping period), and last at rest for 5 min. (recovery period). The number of MSNA bursts per min. (burst rate) in the group with myelopathy was more than that in the control group (p < 0.05) in all three periods. The response by MSNA to handgripping in the group with myelopathy was higher than that in the control group at the start of handgripping (p < 0.01), and tended to be higher even 5 min. after handgripping ended. The results appeared to demonstrate that MSNA of patients with mild myelopathy for which surgery is indicated is increased in the lower extremities.     

I1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives

Moxonidine is an I1-imidazoline receptor agonist that reduces blood pressure in hypertensives. Experimental data suggest that moxonidine inhibits central sympathetic activity. However, whether such a mechanism is involved in vivo in humans is still unclear. We investigated the effects of 0.4 mg moxonidine orally on muscle sympathetic nerve activity and heart rate in an open study in 8 healthy volunteers. Furthermore, we studied the effects of 0.4 mg moxonidine on muscle sympathetic nerve activity, heart rate, blood pressure, 24-hour blood pressure profile, and hormone plasma levels in 25 untreated hypertensives in a double-blind, placebo-controlled study. Moxonidine decreased muscle sympathetic nerve activity in both healthy volunteers (P<0.05 versus baseline) and hypertensives (P<0.02 versus placebo). Plasma norepinephrine also decreased (P<0. 01), whereas plasma epinephrine and renin levels did not change (P=NS). Furthermore, moxonidine decreased systolic (P<0.0001) and diastolic (P<0.001) blood pressure. Heart rate decreased after moxonidine in healthy subjects (P<0.05); in hypertensives, heart rate decreased during the night hours (P<0.05) but not during daytime (P=NS). Plasma levels of LDL, HDL, and total cholesterol were not influenced by the drug (P=NS). Moxonidine decreases systolic and diastolic blood pressure by inhibiting central nervous sympathetic activity. This makes this new drug suitable for the treatment of human hypertension and possibly for other cardiovascular diseases with increased sympathetic nerve activity, ie, ischemic heart disease and heart failure.     

Effects of microinjection of L-NNA and SNP into ventrolateral medulla on blood pressure, heart rate and renal sympathetic nerve activity in rats

The effects of microinjection of a NO synthase inhibitor--N-nitro-L-arginine (L-NNA) and NO donor-sodium nitroprusside (SNP) into ventrolateral medulla on blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were examined in anesthetized rats to define the role of L-arginine: NO pathway in the central regulation of BP and to explore the underlying mechanism. The results obtained were as follows: (1) Following microinjection of L-NNA into rostral ventrolateral medulla (RVLM), both of MAP and RSNA were increased. The effects lasted for more than 30 min and could be reversed by prior intravenous injection of L-arginine. (2) In response to microinjection of SNP into RVLM, MAP and RSNA were decreased, while HR showed no significant change. (3) During microinjection of L-NNA into caudal ventrolateral medulla (CVLM), MAP, HR and RSNA were decreased. (4) Upon injection of SNP into CVLM, MAP and RSNA were increased, but HR showed no significant change. The above-mentioned results indicate that the L-arginine: NO pathway may exhibit a modulatory action on the activity of ventrolateral medulla neurons.     

Respiratory responses in heat-exposed rabbits: inhibition of tachypnoea offset by increase in tidal volume

Rabbits in which thermal panting has been inhibiting by previous cold exposure or by water deprivation respond to a raised ambient temperature with an increase in tidal volume. By so doing, they are able to maintain a minute volume appropriate to their thermoregulatory requirements.     

Reflex control of cardiac sympathetic nerve activity in anesthetized rats

Reflex control of sympathetic outflow to the heart was evaluated by recording the efferent discharges of the interior cardiac sympathetic nerves in anesthetized rats. The reflex responses of inferior cardiac sympathetic nerve activity (ICNA) to arterial baroreceptor loading by phenylephrine and to arterial/atrial baroreceptor unloading by hemorrhagic hypotension were compared with those of renal sympathetic nerve activity (RNA) and adrenal sympathetic nerve activity (ANA). The reflex decrease in ICNA to the phenylephrine-induced graded increase in arterial blood pressure was smaller than that of RNA or ANA. Thus ICNA is less sensitive to arterial baroreceptor stimulation. Hemorrhage produced a volume-dependent decrease in ICNA. The response was significantly smaller than that in RNA and was directionally opposite to that in ANA. Cervical vagotomy but not sinoaortic denervation abolished the hemorrhage-induced ICNA response, suggesting an important role of vagal pathways. These findings demonstrate that the reflex responses of sympathetic outflow to the heart were quantitively and qualitatively different from those to the kidney and the adrenal gland, indicating the regional control of sympathetic nerve activity in the regulation of cardiovascular functions.     

Role of the splanchnic nerve in hypotension induced by acute obstructive suppurative cholangitis

A model of acute suppurative cholangitis with septicemia but without shock was made in 14 rabbits. Fourty-eight hours afterwards, reoperation was performed with the right major splanchnic nerve and right celiac plexus exposed for monitoring. A catheter with an inflatable rubber bag was inserted into the common bile duct via the duodenum for injection with water into the rubber bag to produce a biliary high pressure of 20 kPa, which was subsequently maintained for 2 hours. The right major splanchnic nerve impulse frequency was found significantly increased (P < 0.01). The study shows that the fall of blood pressure or shock in the early stage of acute obstructive suppurative cholangitis is induced predominantly by acute biliary hypertension, and our findings would be complementary to Reynolds' hypothesis of the production of shock.     

Baroreflex control of muscle sympathetic nerve activity is attenuated in the elderly

To determine whether the baroreflex control of sympathetic nerve activity is attenuated in the elderly, muscle sympathetic nerve activity (MSNA) from the tibial nerve was monitored using microneurography, and heart rate and blood pressure were recorded during the depressor (phase II) or pressor (phase IV) period to Valsalva's maneuver in 10 younger subjects and 7 aged subjects. The baroreflex slope for heart rate showed attenuation in the aged subjects during the pressor phase but not during the depressor phase, the baroreflex slope for MSNA was also attenuated in the aged subjects during the pressor and tended to be attenuated during the depressor phases. These data suggest impaired baroreflex function for both heart rate and sympathetic nerve activity in the elderly.     

Pressure-independent inhibition of sympathetic activity by noradrenaline: role of baroreceptor C fibres

The effect of i.v. infusion of noradrenaline on activity in the renal sympathetic nerve was studied in rabbits anesthetized with chloralose and urethane. Noradrenaline (3--8 microgram/kg-min) initially increased mean arterial pressure 20--40 mmHg and consequently reduced renal nerve activity. However, studies over a wide range of pressures--obtained by changing the blood volume, revealed that noradrenaline after a few minutes had induced a pressure-independent reduction of sympathetic discharge. The effect disappeared with baroreceptor denervation. An unchanged relationship between arterial pressure and integrated activity in the whole left aortic nerve (which is largely a measure of activity in A fibres) suggested that the sympathetic depression was due to excitation of aortic nerve C fibres. This conclusion was supported by studies of sympathetic responses to selective stimulation of aortic nerve A and C fibres at equal pressures before and during infusion of noradrenaline. Compared to the reflex activity from A fibres, C fibre stimulation was invariably less effective in suppressing renal nerve activity during the infusion. Our studies indicate that noradrenaline may effect a negative feedback control of sympathetic discharge through activation of baroreceptor C fibres.     

Physical training and baroreceptor control of sympathetic nerve activity in humans

In nine sedentary subjects (16.5 +/- 0.4 years, mean +/- SEM) we measured blood pressure (Finapres device), heart rate (electrocardiogram), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) at rest and during intravenous infusion of phenylephrine and nitroprusside. These measurements were performed before and after 10 weeks of endurance training (2 h/d, 5 d/wk) that increased maximum oxygen consumption from 34.8 +/- 2.1 to 40.4 +/- 1.8 mL/kg per minute (P < .02). Basal mean blood pressure and muscle sympathetic nerve activity were lower after than before endurance training (86.5 +/- 2.6 versus 97.5 +/- 1.8 mm Hg, P < .05, and 14.0 +/- 1.8 versus 21.2 +/- 2.3 bursts per minute, P < .02), and the changes in these variables were closely related (r = .95, P < .01). Similar mean blood pressure increases induced by phenylephrine caused greater reductions in heart rate and muscle sympathetic nerve activity after than before endurance training (-8.6 +/- 0.8 versus -6.1 +/- 1.1 beats per minute, P = NS, and -78.0 +/- 4.6% versus -53.6 +/- 4.8%, P < .05). Likewise, similar mean blood pressure reductions induced by nitroprusside caused greater increases in heart rate and muscle sympathetic nerve activity after than before endurance training (18.6 +/- 3.0 versus 12.4 +/- 2.4 beats per minute, P < .05, and 128.1 +/- 26% versus 63.2 +/- 11%, P < .02). No alteration in hemodynamics, oxygen consumption, muscle sympathetic nerve activity, and baroreceptor reflex sensitivity occurred in four other age-matched sedentary subjects studied before and after a 10-week observation period without endurance training.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of alpha- and beta-adrenoceptor blockade on purine secretion induced by sympathetic nerve stimulation in the rat kidney

To characterize the effects of renal sympathetic nerve activation (RSNA) on renal purine secretion, 13 perfused rat kidneys were stimulated with periarterial electrodes at 7 Hz for 3 min, and purine secretion was determined by measuring with high-performance liquid chromatography purines in the renal venous perfusate 1 min before and during the last minute of RSNA. RSNA significantly increased renal perfusion pressure and significantly increased the secretion of adenosine and adenosine metabolites (inosine, hypoxanthine, and xanthine) by 2- to 5-fold. To investigate the participation of alpha- and beta-adrenoceptors in this response, four groups of perfused kidneys (n = 5/group) were pretreated with either vehicle, prazosin (alpha1-adrenoceptor antagonist; 0.03 microM), phentolamine (alpha1/2-adrenoceptor antagonist; 3 microM), or propranolol (beta1/2-adrenoceptor antagonist; 0.1 microM), and purine secretion was measured before and during RSNA at 1, 3, 5, 7, and 9 Hz. Prazosin, phentolamine, and propranolol abolished the RSNA-induced increase in the secretion of adenosine, inosine, hypoxanthine, and xanthine. In contrast, prazosin and phentolamine nearly abolished, whereas propranolol only slightly reduced, renal vascular responses to RSNA. Our results indicate that RSNA increases renal purine secretion via a mechanism that requires both alpha- and beta-adrenoceptors. It is well known that in the kidney adenosine activates renal afferent nerves, enhances renovascular responses to norepinephrine and angiotensin II, and increases sodium reabsorption; therefore, RSNA-induced adenosine production may contribute to the hypertensive effects of RSNA. Moreover, the antihypertensive effects of beta-adrenoceptor antagonists may in part be due to inhibition of RSNA-induced renal adenosine production.     

Age-related changes in sympathetic modulation of sensory nerve activity in rat skin

OBJECTIVES: Sensory nerves play an important role in mediating neurogenic inflammation and subsequent tissue healing. A decrease in sensory nerve function with increasing age has been reported to correlate with poor tissue healing. Sympathetic nerves are known to modulate sensory nerve function, and changes in this modulation could also have important implications with ageing. The aims of this study were to examine the effect of different frequency electrical stimulation (ES) on the microvascular responses obtained to sensory nerve activation in young, aged and capsaicin-pretreated rats and modulation of these responses by sympathetic efferents. METHODS: Using laser Doppler flowmetry, vascular responses to antidromic ES of the sciatic nerve were monitored in the base of vacuum-induced blisters in the hind footpad. The non-selective alpha-adrenoceptor antagonist phentolamine (3 mg/kg, i.v.) was administered 20 min prior to ES. RESULTS: At high frequency ES (20V, 2ms, 15Hz for 1 min), the vascular response in old rats was significantly reduced (46 percent decrease, p < 0.05) compared to young control. At low frequency ES (20 V, 2 ms, 5 Hz for 1 min) however, older rats produced similar vascular responses to the young. Capsaicin-pretreated rats showed significantly reduced vascular responses to both high and low frequency ES, regardless of age. Pretreatment with phentolamine significantly increased the microvascular response in young rats at high (87 percent) and low (36 percent) frequency ES. In contrast, phentolamine significantly increased the ES-induced response in old rats at high frequency only (147 percent increase). CONCLUSIONS: The results suggest that the aged sensory nerve responds preferentially to low frequency ES and that sympathetic efferents exert an inhibitory modulatory effect on the vascular response evoked by sensory nerve stimulation. There are age-related changes in sympathetic modulation of sensory nerve-mediated responses which is dependent on stimulation frequency.     

Effects of insulin on renal function, sympathetic nervous activity and forearm blood flow in normal human subjects

OBJECTIVE: To assess fully the vasodilatory and sodium-retaining effects of insulin. DESIGN: Prospective physiologic study using a dose-response protocol. SETTING: Clinical investigation unit of a tertiary referral hospital. PARTICIPANTS: Six normal, healthy men. INTERVENTIONS: Subjects were given increasing doses of insulin intravenously from 10 to 1200 mU/m2 per minute, using the euglycemic "clamp" technique. OUTCOME MEASURES: Urinary sodium excretion, systemic and renal hemodynamics, plasma norepinephrine levels and forearm blood flow after each dose. RESULTS: Low doses of insulin (up to 20 mU/m2 per minute) produced a significant antinatriuresis (0.18 [SEM 0.05] v. 0.37 mmol per minute at baseline, p < 0.01) and antidiuresis (2.53 [SEM 0.67] v. 6.21 [SEM 1.66] mL per minute, p < 0.01) with no associated changes in renal hemodynamics or sympathetic nervous activity. Subsequent higher doses of insulin improved urinary volume and sodium excretion to above baseline levels associated with renal and forearm vasodilatation, although mean arterial pressure remained unaltered. CONCLUSIONS: Hyperinsulinemia initially causes an antinatriuresis and antidiuresis through a direct action on the renal tubule. The subsequent phenomenon of escape from renal sodium retention may serve as a regulatory mechanism on sodium homeostasis in conditions associated with hyperinsulinemia and sodium retention.     

Effects of brovincamine fumarate on choroidal blood volume in rabbits]

We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits.