Adrenomedullary secretion of epinephrine is increased in mild essential hypertension

To assess whether patients with mild essential hypertension have excessive activities of the sympathoneuronal and adrenomedullary systems, we examined total body and forearm spillovers and norepinephrine and epinephrine clearances in 47 subjects with mild essential hypertension (25 men, 22 women, aged 38.1 +/- 6.7 years) and 43 normotensive subjects (19 men, 24 women, aged 36.5 +/- 5.9 years). The isotope dilution method with infusions of tritiated norepinephrine and epinephrine was used at rest and during sympathetic stimulation by lower body negative pressure at -15 and -40 mm Hg. Hypertensive subjects had a higher arterial plasma epinephrine concentration (0.20 +/- 0.01 nmol.L-1: mean +/- SE) than normotensive subjects (0.15 +/- 0.01) (P < .01). The increased arterial plasma epinephrine levels appeared to be due to a higher total body epinephrine spillover rate in the hypertensive subjects (0.23 +/- 0.02 nmol.min-1.m-2) than the normotensive subjects (0.18 +/- 0.01) (P < .05) and not to a decreased plasma clearance of epinephrine. The arterial plasma norepinephrine level, total body and forearm norepinephrine spillover rates, and plasma norepinephrine clearance were not altered in the hypertensive subjects. The responses of the catecholamine kinetic variables to lower body negative pressure were not consistently different between normotensive and hypertensive individuals. These data indicate that individuals with mild essential hypertension (1) have elevated arterial plasma epinephrine concentrations that are due to an increased total body epinephrine spillover rate, indicating an increased adrenomedullary secretion of epinephrine; (2) have no increased generalized sympathoneuronal activity and no increased forearm norepinephrine spillover; and (3) have similar responses of both the sympathoneuronal and adrenomedullary systems to sympathetic stimulation by lower body negative pressure.     

Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events

We studied the effects of cigarette smoking, sham smoking and smoking during adrenergic blockade in 10 subjects to determine whether smoking released the sympathetic neurotransmitter norepinephrine, as well as the adrenomedullary hormone epinephrine, and whether smoking-associated hemodynamic and metabolic changes were mediated through adrenergic mechanisms. Smoking-associated increments in mean (+/- S.E.M.) plasma norepinephrine (227 +/- 23 to 324 +/- 39 pg per milliliter, P less than 0.01) and epinephrine (44 +/- to 113 +/- 27 pg per milliliter, P less than 0.05) were demonstrated. Smoking-associated increments in pulse rate, blood pressure, blood glycerol and blood lactate/pyruvate ratio were prevented by adrenergic blockade; increments in plasma growth hormone and cortisol were not. Since significant smoking-associated increments, in pulse rate, blood pressure and blood lactate/pyruvate ratio, preceded measurable increments in plasma catecholamine concentrations, but were adrenergically mediated, these changes should be attributed to norepinephrine released locally from adrenergic axon terminals within the tissues rather than to increments in circulating catecholamines.     

Brain beta-endorphin and other opioids are involved in restraint stress-induced stimulation of the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system, and the adrenal medulla in the rat

Opiates and opioids have complex effects on the hypothalamic-pituitary-adrenal axis, and they stimulate the sympathetic nervous system. This study was designed to clarify the role of brain beta-endorphin in the mechanism by which stress increases plasma concentrations of adrenocorticotropin (ACTH), epinephrine (E), and norepinephrine (NE). Intracerebroventricular (i.c.v.) administration of beta-endorphin to rats significantly increased plasma ACTH levels at doses of 0.09, 0.3, and 1.5 nmol, and plasma E and NE levels at doses of 0.3 and 1.5 nmol. The rise of plasma ACTH, E, and NE levels by 0.3 nmol beta-endorphin was inhibited by intravenous (i.v.) administration of 2 mg/kg b.wt. naloxone. I.v. administration of anti-rat corticotropin-releasing hormone (CRH) rabbit serum completely blocked the beta-endorphin-induced ACTH secretion without affecting the secretion of E and NE. I.c.v. administration of anti-beta-endorphin rabbit gamma-globulin attenuated a 30-min restraint stress-induced rise of plasma ACTH levels without significant influence on the rise of E and NE levels, whereas i.v. administration of naloxone attenuated the restraint stress-induced rise of plasma ACTH, E and NE levels. These results suggest that i.c.v. administration of beta-endorphin stimulates the secretion of ACTH, E, and NE through opiate receptor, and that brain CRH mediates the beta-endorphin-induced secretion of ACTH. The results also suggest that brain beta-endorphin is, at least in part, involved in the restraint stress-induced stimulation of the hypothalamic-pituitary-adrenal axis, and that some opioids other than beta-endorphin are involved in the stimulatory mechanism of the autonomic nervous system and the adrenal medulla in the rat.     

Catecholamine responses to short-term high-intensity resistance exercise overtraining

Seventeen weight-trained males were divided into an overtraining group [OT; n = 11; age = 22.0 +/- 0.9 (SE) yr] that weight trained their legs daily for 2 wk with 100% 1 repetition maximum relative intensity on a squat machine and a control group (n = 6; age = 23.7 +/- 2.4 yr) that exercised 1 day/wk with low relative intensity (50% 1 repetition maximum). Test batteries including strength assessments and resting and exercise-induced concentrations of epinephrine and norepinephrine were conducted at the beginning, middle, and end (tests 1-3, respectively) of the study. Strength capabilities decreased by test 3 for the OT group (P < 0.05). Resting catecholamine concentrations did not change for either group during the study, whereas exercise-induced concentrations of both epinephrine (test 1 = 3,407.9 +/- 666.6 pmol/l, test 2 = 7,563.7 +/- 1,210.6 pmol/l, test 3 = 6,931.6 +/- 919.3 pmol/l) and norepinephrine (test 1 = 42.9 +/- 7.4 nmol/l, test 2 = 70.0 +/- 8.8 nmol/l, test 3 = 85.2 +/- 14.5 nmol/l) significantly increased by tests 2 and 3 for only the OT group. Correlation coefficients suggested decreased responsitivity of skeletal muscle to sympathetic nervous system activity. It appears that altered exercise-induced sympathetic nervous system activity accompanies high relative intensity resistance exercise overtraining and may be among the initial responses to the onset of the previously theoretical sympathetic overtraining syndrome.     

Histological and urographic findings in the autotransplanted ureter without kidney in dogs: preliminary report

To ascertain whether isoflurane produces a peripheral splanchnic sympathectomy as compared to fentanyl or pentobarbital anesthesia, 12 mongrel dogs (30-45 kg) were allocated randomly to one of three anesthetic test groups, tracheally intubated, surgically prepared, and subjected to unilateral electrical stimulation of the greater splanchnic nerve. Anesthetically, Group 1 animals (n = 4) received pentobarbital, Group 2 animals (n = 4) were administered fentanyl, and Group 3 animals (n = 4) received isoflurane. Stimulation continued for 90 min. Each second of stimulation consisted of 20 stimuli of 0.5 minimum alveolar anesthetic concentration duration and 5 V intensity, delivered during a 0.2-s interval, followed by an 0.8-s pause. To assess splanchnic sympathetic responses, mean arterial blood pressure, heart rate, pulmonary artery diastolic, cardiac output, adrenal blood flow, adrenal and arterial norepinephrine (N) and epinephrine (E) were obtained before and at 5, 10, 15, 30, 45, 60, and 90 min during stimulation. In Group 1 animals (pentobarbital), electrical stimulation elicited marked increases in mean arterial blood pressure, pulmonary artery diastolic, and cardiac output (P < 0.001). Examination of the adrenal effluent, which was exteriorized from the animal during the protocol, revealed that adrenal blood flow, adrenal vein N and E concentrations dramatically increased (P < 0.0001). Arterial N and E concentrations remained unchanged. Results of Group 2 animals (fentanyl) were similar to those of Group 1; mean arterial blood pressure, pulmonary artery diastolic, and cardiac output increased (P < 0.005). Adrenal blood flow, adrenal vein N and E increased dramatically (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The clinical significance of phasic duodenal intubation and ultrasonic monitoring of the gallbladder in healthy subjects

Hypoxic and low-temperature effects on the thermal regulation and the content of catecholamines (epinephrine--E and norepinephrine--NE) in mice have been compared. Continuous and repeated hypoxia brought about a significant drop of the rodent body temperature and heat content. Found was a significant elevation of catecholamines in the pituitary and adrenal tissues, and blood plasma with E prevalence after the continuous exposure. Repeated stimulus resulted in a more pronounced effect. Exception was the adrenal tissue where enhanced E and NE secretion into blood was noted. The uninterrupted and repeated cold conditions were also responsible for heat release. Continuous exposure to low temperature increased NE and decreased insignificantly E in blood and adrenal. Multiple stimulation increased sharply catecholamines concentration in blood plasma with the dominance of epinephrine in the pituitary gland, and norepinephrine in the adrenal.     

Dose-response relationship between plasma epinephrine concentration and alveolar liquid clearance in dogs

Previously, alveolar liquid clearance (ALC) was observed to increase in a canine model of neurogenic pulmonary edema (NPE) by adrenal epinephrine (S. M. Lane, K. C. Maender, N. E. Awender, and M. B. Maron. Am. J. Respir. Crit. Care Med. 158: 760-768, 1998). In this study the dose-response relationship between plasma epinephrine concentration and ALC was determined in anesthetized dogs by infusing epinephrine to produce plasma concentrations of 256 +/- 37, 1,387 +/- 51, 15,737 +/- 2,161, and 363,997 +/- 66,984 (SE) pg/ml (n = 6 for each concentration) for 4 h and measuring the resultant ALC. The latter was determined by mass balance after instillation of autologous plasma into a lower lung lobe. These plasma concentrations produced ALCs of 14.3 +/- 1.2, 20.5 +/- 1.9, 30.1 +/- 1.5, and 37.9 +/- 2.7% of the instilled volume, respectively. ALC after the lowest infusion rate was not different from that previously observed under baseline conditions (14.1 +/- 2.1%), whereas in a previous study of NPE, plasma epinephrine concentration increased to 7,683 +/- 687 pg/ml and ALC was 30.4 +/- 1.6%. These data indicate that, during recovery from canine NPE, ALC is not maximally stimulated and suggest that it might be possible to pharmacologically produce further increases in the rate of resolution of this form of edema.     

Distribution of coronal and root caries experience among persons aged 60+ in South Australia

The time course of the effects of intravenous or intracoronary administration of peptide leukotrienes on metabolic parameters and on systemic and coronary hemodynamics was evaluated in 15 patients with normal coronary arteries. Peptide leukotriene C4 (2 nmol given as a bolus intravenous injection) induced an early fall (at 2 min) in mean arterial pressure (P < 0.02) associated with a rise in heart rate (P < 0.001) and in plasma levels of epinephrine (P < 0.05) and norepinephrine (P < 0.005), but without significant changes in coronary blood flow or coronary vascular resistance. Mean arterial pressure, heart rate, norepinephrine, and epinephrine returned to baseline values 10 min after leukotriene C4 administration. In contrast, at 10 min post leukotriene C4, with coronary blood flow and myocardial oxygen consumption unchanged, an increase in coronary vascular resistance (P < 0.05) and in myocardial oxygen extraction (P < 0.01) was observed, which returned to baseline values at 20 min post leukotriene C4. Peptide leukotriene D4 (3 nmol, given in the left coronary artery) induced an early (20 s) and transient fall in mean arterial pressure (P < 0.001) paralleled by a rise in heart rate and plasma levels of epinephrine and norepinephrine, all of which returned to baseline at 10 min. Coronary vascular resistance increased at 10 and 15 min (P < 0.02 and P < 0.05, respectively) and myocardial oxygen extraction at 15 min (P < 0.02). These results suggest that small doses of peptide leukotrienes induce both an early and transient fall in mean arterial pressure associated with secondary sympathoadrenergic activation, and a late increase in small coronary arteriolar resistance.     

Intracellular signalling by binding sites for the antipsoriatic agent monomethylfumarate on human granulocytes

Basal and stress levels of catecholamines (CA) in the adrenal glands, and circulatory levels of adrenocorticotropic hormone (ACTH) were examined in female Wistar rats aged 1, 3, 10 and 24 months. Our data showed reduction in basal dopamine (DA) concentration in adrenal glands and an increase in this catecholamine in response to stress at all ages (1, 3, 10, 24 months). The greatest levels of basal norepinephrine (NE) and epinephrine (E) concentrations in the adrenal glands were noted in intact rats at the age of 24 months. On the other hand, the stress response of NE and DA had a tendency to fall, reaching basal values at the age of 10 and 24 months of age. Basal circulatory levels of ACTH showed a reduction with age. The stress response of ACTH was reduced in animals aged 10 and 24 months. Reduced basal values of adrenal DA and increased NE and E values, suggest that there is increased adrenomedullar activity at the age of 24 months. On the other hand, the reduced or even absent stress response of NE and E observed in the adrenals, in 10 and 24 months old rats, may be of interest in considering the ability of these animals for adaptation. Basal and stress values of plasma ACTH are significantly reduced with the onset of senescence in female rats.     

Alpha 2-adrenoceptors and I1-imidazoline binding sites: relationship with catecholamines in women of reproductive age

A comparison is presented between plasma catecholamine concentrations and platelet [125I]-p-iodoclonidine binding sites in 16 healthy women. Blood samples were obtained at six regularly spaced intervals over two consecutive menstrual cycles from healthy women with regular menstrual periods. Although no cycle-related changes were observed per se, there were significant correlations between the platelet binding sites and plasma norepinephrine and epinephrine concentrations. The densities of platelet alpha 2-adrenoceptors were negatively correlated in an exponential fashion (r2 = 0.694, P = 0.009) with plasma epinephrine concentrations, implying agonist-induced downregulation. On the other hand, platelet I1-imidazoline binding sites were positively correlated with plasma concentrations of norepinephrine in a linear fashion (r2 = 0.326, P = 0.021). This is the first indication that I1 binding sites might be upregulated by a physiological factor. Furthermore, the data suggest that elevations in plasma norepinephrine might explain reports of upregulated I1 binding sites in depressed patients.     

Hemodynamic and regional blood flow responses to nicotine at rest and during exercise

We hypothesized that nicotine compromises cardiovascular responses to dynamic exercise. Hemodynamic variables were measured in conscious miniswine before and at 2 min of nicotine infusion (20 micrograms.kg-1.min-1; i.a.; N = 6) during resting conditions. Mean arterial pressure elevations (MAP; 14%) and plasma nicotine concentrations (49 +/- 7 ng.ml-1) were similar to those elicited by cigarette smoking in humans. In addition, nicotine increased systemic vascular resistance (SVR; 56%), the heart rate x systolic blood pressure product (RPP; 11%), and regional vascular resistance in the left-ventricular, renal, and splanchnic circulations, while cardiac output decreased (CO; 23%) and skeletal muscle blood flow and vascular resistance were unaffected. Plasma norepinephrine and epinephrine increased by approximately 30% and 90%, respectively. On separate days, the same hemodynamic responses were measured before and at 20 min of treadmill running during vehicle or nicotine infusion for the last 2 min of exercise (N = 10). Nicotine increased MAP (6%), SVR (14%), and RPP (3%), and elevated vascular resistance in the proximal colon and pancreas. Moreover, compared to exercise + vehicle, norepinephrine and epinephrine increased by approximately 13% and 24%, respectively, during exercise + nicotine infusion. These findings suggest that the detrimental effects of nicotine observed at rest are minimized during exercise. Nicotine's effects may be reduced during exercise by competition from local vasodilators in the heart and active musculature, and/or by differing activation of sympathetic nerve activity.     

Influence of circulating epinephrine and norepinephrine on insulin-like growth factor binding protein-1 in humans

The aim of the present study was to investigate the influence of circulating epinephrine (Epi) and norepinephrine (Norepi) on serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations. Healthy men received 0.3 nmol.kg.min Epi iv (n = 6), 0.5 nmol.kg.min Norepi iv (n = 7), or saline (n = 5) during 30 min. Arterial blood samples were obtained before, during, and 120 min after infusion. During the catecholamine infusion arterial Epi and Norepi plasma concentrations reached 6.35 +/- 0.53 and 15.65 +/- 2.71 nmol/L, respectively, which resulted in significant increases in glucose concentrations. When Epi was infused, IGFBP-1 increased from 45 +/- 6 micrograms/L to 76 +/- 10 micrograms/L (P < 0.05) 60 min after the infusion. Epi was also followed by increases in insulin, C-peptide, and glucagon. Norepi resulted in a slight increase in circulating IGFBP-1 (43 +/- 6 to 54 +/- 8 nmol/L, NS). The findings suggest that Epi, at plasma concentrations similar to those reached during physical stress, stimulates the production of IGFBP-1 in humans.     

Release of amino acids and related compounds from the adrenal equivalent and caudal vein of the eel in vitro

The release of catecholamines and cortisol from the perifused adrenal region and caudal vein of the eel (Anguilla rostrata) was compared with the release of 39 amino acids and related compounds. Dopamine, norepinephrine and epinephrine were present in all perifusates of the adrenal region. Dopamine release from the caudal vein exceeded that from the adrenal region, and norepinephrine and epinephrine were not detected. Cortisol was present in the perifusate of the adrenal region but virtually absent in caudal vein perifusate. Of the six substances with known or suspected neurotransmitter function, taurine, aspartate, glutamate, glycine and alanine were present in all or almost all samples from both the adrenal equivalent and the caudal vein. gamma-aminobutyric acid (GABA) was detected in a few samples from either preparation. The release of taurine and phosphoethanolamine may be linked to that of norepinephrine and epinephrine. Adrenocorticotropic hormone (ACTH) enhanced the release of cortisol, aspartate, valine, leucine and ornithine from the adrenal region, but the release appears to be from differing sources or cellular pools. Overall, the study revealed that both the adrenal region and caudal vein release a large number of amino acids and related substances. The caudal vein, and possibly other blood vessels as well, may be a major source of circulating dopamine.     

Norepinephrine release in the human forearm: effects of epinephrine

It has been postulated that delayed facilitation of norepinephrine release by epinephrine is causally related to the development of hypertension. It has been proposed that a brief increase in epinephrine concentrations results in the uptake of epinephrine into the sympathetic nerve terminal. Subsequent rerelease of epinephrine stimulates presynaptic beta-adrenergic receptors, resulting in a prolonged increase in plasma norepinephrine (NE) concentrations, with amplified sympathetic responses and vasoconstriction. To determine whether such epinephrine-induced, delayed facilitation of NE release occurs in a vascular bed draining resistance vessels and, if it occurs, whether that facilitation differs in hypertension, we used a radioisotope dilution method to measure unstimulated and isoproterenol-stimulated forearm NE spillover before, during, and after a 50 ng/min infusion of epinephrine for 30 minutes directly into the brachial artery. No delayed facilitatory effects of epinephrine on forearm NE spillover were observed in either 6 normotensive (NT) or 8 borderline hypertensive (BHT) subjects (NT unstimulated forearm NE spillover preepinephrine 1.79+/-0.41 ng/min versus postepinephrine 2.36+/-0.65 ng/min, P=.38; BHT preepinephrine 2.24+/-0.70 ng/min versus postepinephrine 1.93+/-0.46 ng/min, P=.51; NT isoproterenol-stimulated forearm NE spillover preepinephrine 4.61+/-1.01 ng/min versus postepinephrine 4.4+/-0.98 ng/min, P=.9; BHT preepinephrine 4.04+/-1.36 ng/min versus postepinephrine 4.69+/-1.49 ng/min P=.5). We conclude that the short-term local infusion of epinephrine does not have a delayed facilitatory effect on forearm NE spillover in NT or BHT subjects. Therefore, the prolonged increase in NE concentrations after epinephrine infusion previously shown systemically, and not seen locally in the forearm, suggests that the delayed facilitatory response to epinephrine may occur in other organs.     

Isoflurane and sevoflurane augment norepinephrine responses to surgical noxious stimulation in humans

BACKGROUND: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. METHODS: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. RESULTS: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. CONCLUSION: The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.     

4-OH amphetamine enhances retention of an active avoidance response in rats and decreases regional brain concentrations of norepinephrine and dopamine.

In Exp I, an .82 mg/kg dose of 4-OH amphetamine hydrobromide (AMP) administered ip immediately following training in a 1-way active avoidance task enhanced retention performance of male ARS Sprague-Dawley rats measured 24 hrs later. In contrast, AMP in a dose range of .41–2.64 mg/kg, ip, did not affect retention of a swim escape task (Exp II). The behaviorally active dose of .82 mg/kg decreased dopamine concentrations in the amygdala and hippocampus. A dose of 8.2 mg/kg administered ip to naive untrained Ss (Exp III) decreased concentrations of norepinephrine measured in the amygdala, cortex, hippocampus, hypothalamus, and midbrain; decreased concentrations of dopamine in the amygdala, cortex, hippocampus, and striatum; and significantly reduced concentrations of norepinephrine and epinephrine in the adrenal medulla. In addition, because the integrity of the adrenal medulla is necessary for the enhancing action of AMP and because AMP reduces concentrations of catecholamines in the brain and adrenal medulla, it is possible that this drug affects retention performance by a dual action on the brain and the adrenal medulla. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decreased epinephrine responses to hypoglycemia during sleep

BACKGROUND: In patients with type I diabetes mellitus, hypoglycemia occurs commonly during sleep and is frequently asymptomatic. This raises the question of whether sleep is associated with reduced counterregulatory-hormone responses to hypoglycemia. METHODS: We studied the counterregulatory-hormone responses to insulin-induced hypoglycemia in eight adolescent patients with type I diabetes and six age-matched normal subjects when they were awake during the day, asleep at night, and awake at night. In each study, the plasma glucose concentration was stabilized for 60 minutes at approximately 100 mg per deciliter (5.6 mmol per liter) and then reduced to 50 mg per deciliter (2.8 mmol per liter) and maintained at that concentration for 40 minutes. Plasma free insulin, epinephrine, norepinephrine, cortisol, and growth hormone were measured frequently during each study. Sleep was monitored by polysomnography. RESULTS: The plasma glucose and free insulin concentrations were similar in both groups during all studies. During the studies when the subjects were asleep, no one was awakened during the hypoglycemic phase, but during the final 30 minutes of the studies when the subjects were awake both the patients with diabetes and the normal subjects had symptoms of hypoglycemia. In the patients with diabetes, plasma epinephrine responses to hypoglycemia were blunted when they were asleep (mean [+/-SE] peak plasma epinephrine concentration, 70+/-14 pg per milliliter [382+/-76 pmol per liter]; P=0.3 for the comparison with base line), as compared with when they were awake during the day or night (238+/-39 pg per milliliter [1299+/-213 pmol per liter] P=0.004 for the comparison with base line, and 296+/-60 pg per milliliter [1616+/-327 pmol per liter], P=0.004, respectively). The patients' plasma norepinephrine responses were also reduced during sleep, whereas their plasma cortisol concentrations did not increase and their plasma growth hormone concentrations increased slightly. The patterns of counterregulatory-hormone responses in the normal subjects were similar. CONCLUSIONS: Sleep impairs counterregulatory-hormone responses to hypoglycemia in patients with diabetes and normal subjects.     

Novel protein toxin-based strategy for development of cytotoxic T lymphocyte vaccines

Unexplained episodic hypertension, hypotension, or orthostatic intolerance, tachycardia, anxiety, and flushing in 21 patients were investigated for the possibility of hypovolemia by blood volume and individual plasma catecholamines (including autocrine paracrine-born dopamine), determinations baseline, in response to upright posture and catecholamines only during the episodic blood pressure swings. Blood volume was determined by Cr51 fixed to patients' hemoglobin, free norepinephrine, epinephrine, and dopamine with dopamine sulfate following sulfatase hydrolysis, radioenzymatically. The recumbent mean 27.4+/-3% (SE) blood volume decrease from predicted values accentuating to 33.5+/-4% upright was associated with normal baseline plasma free norepinephrine, epinephrine, dopamine, dopamine sulfate, plasma renin activity, and aldosterone with normal mean postural responses from all patients except a hyperresponsive compared to controls (p < 0.04), plasma renin activity increase from 0.657+/-0.1 to 4.47+/-1.8 ng/mL/hr. During the hypertensive, hypotensive, or tachycardic episodes the moderate increase of free norepinephrine and epinephrine (p < 0.04) (but not free dopamine) contrasted with an increase of dopamine sulfate from 2.5+/-0.9 to clearly pathological values of 16.8+/-8.3 ng/mL (p < 0.0003 on % increase of individual values). We conclude that the normal (but to the degree of hypovolemia inappropriately low orthostatism- and episodes-associated sympathetic arousal) is outpaced by considerable episodic dopamine sulfate surges, reflecting extraneuronal dopamine discharge. Whether this increase contributes to the increased natriuresis directly or by inhibiting aldosterone response to renin-angiotensin, perpetuating hypovolemia, remains to be established.     

Local regulation of collateral ventilation by oxygen and carbon dioxide

The effects of changes in CO2 and O2 on the mechanics of collateral ventilation were studied in anesthetized paralyzed dogs. A doublelumen catheter was wedged into a peripheral airway obstructing a segment of lung distal to the catheter. Through one lumen of the catheter, air, 5% CO2 in air, 10% CO2 in air, 5% O2 in N2, or 5% CO2 in N2 was infused at a constant flow (V). Pressure (Ps) was monitored through the other lumen. At functional residual capacity the resistance to collateral flor Rcoll = Ps/V. When V was interrrupted , the time for Ps to fall 63% was defined as the time constant for collateral ventilation, Tcoll. The effective compliance (Cs') = Tcoll/Rcoll. When air was replaced by 5% CO2, Rcoll fell 46.3% (+/- SE 2.8) and Tcoll fell 41.5% (+/- SE 3.0). When the CO2 concentration was increased from 5% to 10%, Rcoll fell an additional 9.2% (+/- SE 2.2) and Tcoll fell an additional 5.1% (+/- SE 4.4). When air was replaced by 5% O2 in N2, Rcoll rose 36.6% (+/- SE 6.0) and Tcoll rose 13.6% (+/- SE 10.5). No significant changes in Cs' were noted. We conclude that varying concentrations of CO2 and O2 provide potent mechanisms for the control of collateral ventillation which may be of importance in the regulation of ventillation perfusion relationships at the local level.