Static exercise-induced increase in blood pressure in individuals with cervical spinal cord injury

OBJECTIVE: To compare the pressor response to static exercise in subjects with cervical spinal cord injury (SCI) at the C6 to C8 level with that in able-bodied control subjects. In these SCI subjects, the descending supraspinal sympathetic neurons and afferent pathways from the contracting muscles to peripheral vessels via the medullary cardiovascular center are damaged. DESIGN: Mean arterial blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, renin activity, vasopressin, aldosterone, and human atrial natriuretic peptide were measured during a 2-minute period of sustained contraction of elbow flexor group muscle in 7 SCI subjects and 7 age-matched able-bodied control subjects. RESULTS: Static exercise resulted in a significant increase in mean blood pressure (p<.05) in both SCI subjects (pre-exercise. 74.7+/-2.2 mm Hg; static exercise, 81.9+/-4.1 mm Hg) and control subjects (pre-exercise, 101.0+/-4.2 mm Hg; static exercise, 117.0+/-4.9 mm Hg). In SCI subjects, there was no change in heart rate during exercise, whereas in control subjects heart rate increased during exercise (p<.05) (pre-exercise, 8.7+/-3.8 beats/min: static exercise, 76.0+/-3.1 beats/min). There were no significant changes in the hormone levels in the SCI subjects throughout the experiment. CONCLUSION: The significant increase in mean blood pressure observed in the present study indicates the presence of peripheral control from muscle receptors and evoked pressor response during static exercise in SCI subjects.     

Increased norepinephrine levels during catheterization in patients with spinal cord injury.

The hypothesis for this study was that catecholamine levels increase during urinary catheterization in human patients with spinal cord injury. Catecholamine levels, blood pressure, and pulse were measured prospectively in 40 subjects at baseline and during urinary catheterization. Results showed a significant increase in norepinephrine levels from baseline 245 +/- 240 pg (standard deviation (SD)) to 314 +/- 311 pg (SD) during catheterization (P = 0.018, Wilcoxon's). Results also showed a nonsignificant increase in epinephrine levels from baseline (56 +/- 70 pg, SD) to catheterization (84 +/- 125 pg, SD; P = 0.35, Wilcoxon's). Systolic blood pressure increased from 114 to 124 mm Hg (P = 0.004, paired t test). Diastolic blood pressure increased from 75 to 78 mm Hg (P = 0.11, paired t test). There was no significant change in diastolic blood pressure or pulse (P = 0.11 and P = 0.29, respectively, paired t test). In conclusion, norepinephrine levels increased during catheterization in patients with spinal cord injury. Knowledge of catecholamine levels in this process may assist in determining both pathophysiology and potential pharmacologic treatment options in future studies.     

The cold pressor test: pharmacological and therapeutic aspects.

In this review article we discuss several aspects of the physiology, diagnosis, and pharmacology of the cold pressor test. The cold pressor test has been used for the diagnosis of cardiovascular reactivity in normotensive and hypertensive subjects. Some authors have stated that the cold pressor test will identify normotensive candidates at future risk of suffering from hypertensive disease. Interestingly, not all antihypertensive drugs block the exaggerated pressor response induced by cold stress. The most beneficial compounds belong to the alpha- and beta-blocker groups. Furthermore, several neurohormones such as norepinephrine, endothelins, prostaglandins, and angiotensin II have been reported to be released during cold exposure. The neurophysiology of cold pressor test indicates that after stress a great sympathetic discharge is induced at the spinal cord and terminal endings of the sympathetic nervous system. The release of norepinephrine is the cause of arteriolar vasoconstriction and elevation of blood pressure.     

Effects of enalapril maleate on blood pressure, renin-angiotensin-aldosterone system, and peripheral sympathetic activity in essential hypertension

Recent experimental studies showed that inhibition of angiotensin II synthesis may reduce sympathetic activity as evaluated by plasma catecholamine assay, sharing in the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. Fifteen patients with essential hypertension were studied. Blood pressure and heart rate were evaluated both at rest and after stressor laboratory tests, before and four hours after administration of 20 mg of enalapril maleate and on the 14th and 120th days of continued administration. At the same time, blood samples were drawn for determinations of plasma renin activity, ACE, angiotensin II, plasma aldosterone concentration, and plasma norepinephrine levels. Enalapril in a dosage of 20 mg/day significantly and progressively lowered systolic and diastolic blood pressure at rest, with maximal decreases observed on the 120th day of the study period (P less than 0.001). Heart rate at rest and after exercise showed no significant differences throughout the study period. Good blood pressure control was observed during stressor laboratory tests. The greatest impact of blood pressure was observed on the 120th day during dynamic exercise (mean blood pressure from 139 +/- 3.9 to 111.5 +/- 6.3 mmHg; P less than 0.01) and on the 14th day during the cold pressure test (mean blood pressure from 133.3 +/- 3.9 to 111.2 +/- 4.7 mmHg; P less than 0.005). A marked and persistent ACE inhibition and a gradual and progressive decrease of angiotensin II (from 12.42 +/- 2.15 to 5.45 +/- 1.68 pg/ml; P less than 0.005) characterized the humoral activity of enalapril maleate. Moreover, a significant decrease of plasma norepinephrine levels was observed during the follow-up period with maximal reduction on the 120th day (from 311 +/- 34 to 197 +/- 33 pg/ml; P less than 0.01). It has been demonstrated that the pressor effect of angiotensin II was blunted during exercise. Our hemodynamic and humoral results appear to confirm the hypothesis that enalapril maleate may reduce blood pressure by direct inhibition of ACE and of kininase II as well as by a decreased sympathetic output, which may be secondary to angiotensin II inhibition. These results agree with the recent experimental demonstration of a reduced sympathetic nervous response to nerve stimulation during ACE inhibition.     

Cardiovascular responses and postexercise hypotension after arm cycling exercise in subjects with spinal cord injury

OBJECTIVE: To examine postexercise hypotension and contributing factors in subjects with spinal cord injury (SCI). DESIGN: Prospective clinical research study. SETTING: Rehabilitation center. PARTICIPANTS: Subjects with chronic cervical-level (n=19) and thoracic-level (n=8) SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects underwent graded arm-cycling with electrocardiogram and oxygen uptake monitoring to exhaustion. Heart rates and blood pressures were measured before and after exercising. Injury to motor and sensory pathways was determined by American Spinal Injury Association grade, and to autonomic pathways by sympathetic skin responses (SSRs) (n=16). RESULTS: Resting blood pressures and heart rates were lower in cervical than thoracic SCI (mean arterial pressure [MAP]: cervical, 76.6+/-2 mmHg; thoracic, 93.5+/-3 mmHg; P<.001). Following exercise, heart rate responses were greater in thoracic than cervical SCI; MAP increased in thoracic SCI (8.4+/-5 mmHg) and markedly decreased in cervical SCI (-9.3+/-2 mmHg) (P<.001). No subject had significant electrocardiographic abnormalities at rest or during exercise. There were correlations between SSR and heart rate and blood pressure responses to exercise; the correlation between the SSR and blood pressure response was due to an interaction between the heart rate and blood pressure responses. CONCLUSIONS: Abnormal cardiovascular responses to exercise and transient postexercise hypotension were common in cervical, but not thoracic SCI. This may be partly related to loss of descending sympathetic nervous control of the heart and vasculature following high SCI.     

Effects of the angiotensin II receptor antagonist Losartan (DuP 753/MK 954) on arterial blood pressure, heart rate, plasma concentrations of angiotensin II and renin and the pressor response to infused angiotensin II in the salt-deplete dog.

1. The blood pressure, heart rate, hormonal and pressor responses to constant rate infusion of various doses of the angiotensin (type 1) receptor antagonist Losartan (DuP 753/MK 954) were studied in the conscious salt-deplete dog. 2. Doses in the range 0.1-3 micrograms min-1 kg-1 caused no change in blood pressure, heart rate or pressor response to angiotensin II (54 ng min-1 kg-1), and a dose of 10 micrograms min-1 kg-1 had no effect on blood pressure, but caused a small fall in the pressor response to angiotensin II. Infusion of Losartan at 30 micrograms min-1 kg-1 for 3 h caused a fall in mean blood arterial pressure from baseline (110.9 +/- 11.2 to 95.0 +/- 12.8 mmHg) and a rise in heart rate (from 84.6 +/- 15.1 to 103 +/- 15.2 beats/min). Baseline plasma angiotensin II (42.5 +/- 11.8 pg/ml) and renin (64.5 +/- 92.7 mu-units/ml) concentrations were already elevated in response to salt depletion and rose significantly after Losartan infusion to reach a plateau by 70 min. The rise in mean arterial blood pressure after a test infusion of angiotensin II (35.3 +/- 11.6 mmHg) was reduced at 15 min (11.8 +/- 6.8 mmHg) by Losartan and fell progressively with continued infusion (3 h, 4.3 +/- 3.3 mmHg). The peak plasma angiotensin II concentration during infusion of angiotensin II was unaffected by Losartan, but the rise in plasma angiotensin II concentration during infusion was reduced because of the elevated background concentration. Noradrenaline infusion caused a dose-related rise in mean blood arterial pressure (1000 ng min-1 kg-1, +19.9 +/- 8 mmHg; 2000 ng min-1 kg-1, +52.8 +/- 13.9 mmHg) with a fall in heart rate (1000 ng min-1 kg-1, -27.9 +/- 11.5 beats/min; 2000 ng min-1 kg-1, -31.2 +/- 17.3 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Venous responsiveness to norepinephrine in healthy subjects: effects of single doses of 325 mg aspirin

BACKGROUND: Antithrombotic doses of aspirin, which are widely used in patients with cardiovascular disease, may inhibit prostaglandin synthesis but the physiologic significance with regard to vascular tone is not well defined. We hypothesized that inhibition of vasodilator prostaglandin synthesis by aspirin would significantly increase sympathetic-mediated venoconstriction. METHODS: Twelve healthy volunteers (mean age, 24.5 +/- 0.8 years; age range, 19 to 30 years) were studied on two mornings approximately 7 days apart and not less than 90 minutes after a randomized single dose of 325 mg aspirin or matching placebo. Distension of dorsal hand veins was measured with use of the linear variable differential transformer technique during local infusions of exogenous norepinephrine (0.125 to 1,024 ng/min) and during release of endogenous norepinephrine from sympathetic activation by a forehead cold pressor test. Hemodynamic parameters and venous plasma catecholamine levels were measured. Antiplatelet activity of the dose of aspirin was confirmed in three subjects. RESULTS: Aspirin increased venoconstriction to norepinephrine, causing a significant shift to the left (P < .03) of the norepinephrine dose-response curve and a significant decrease in logED50 (P < .03), representing a decrease in the dose of norepinephrine required to reduce vein distension by 50% from 50 to 25 ng/min. Venoconstriction to the cold pressor test was significantly increased by aspirin (10% +/- 3% versus 3% +/- 1% for placebo; P < .02). Cold pressor-induced increases in mean arterial pressure were significantly larger with aspirin compared with placebo (18 +/- 1 versus 14 +/- 1 mm Hg, respectively; P < .03). Baseline levels and stress-induced increases in plasma norepinephrine were not different between days. CONCLUSIONS: The results suggest that aspirin inhibits the role of vasodilator prostaglandins in modulating peripheral venoconstriction and increases vascular resistance during physiologic stress in young healthy subjects.     

Influence of St John's wort on catecholamine turnover and cardiovascular regulation in humans

BACKGROUND: St John's wort (Hypericum perforatum) is a popular over-the-counter antidepressant. Its antidepressive effect has been attributed in part to inhibition of monoamine transporters and monoamine oxidase, on the basis of in vitro studies. METHODS: In a double-blind, randomized, placebo-controlled, crossover study, 16 healthy subjects (11 men and 5 women; mean age, 31 +/- 5 years) ingested either St John's wort (300 mg three times daily) or placebo for 7 days. Imipramine treatment (50 mg three times daily) in 7 subjects served as a positive control. After treatment, physiologic and biochemical tests included cardiovascular reflex testing, graded head-up tilt testing, and plasma catecholamine determinations. RESULTS: St John's wort had no effect on blood pressure, heart rate, heart rate variability, or blood pressure variability, regardless of the test condition. St John's wort had no effect on plasma concentrations of norepinephrine and its main metabolite, dihydroxyphenylglycol, whereas plasma dihydroxyphenylacetic acid (DOPAC; the main metabolite of dopamine) concentrations increased in every subject (1661 +/- 924 pg/mL versus 1110 +/- 322 pg/mL with placebo, P=.04). In contrast, imipramine increased resting blood pressure (124 +/- 10 mmHg/71 +/- 5 mmHg versus 110 +/- 8 mmHg/61 +/- 6 mmHg with placebo, P=.005 for systolic values and P=.003 for diastolic values) and heart rate (74 +/- 7 beats/min versus 62 +/- 6 beats/min with placebo, P=.005) and elicited a marked orthostatic tachycardia (increase in heart rate of 43 +/- 17 beats/min versus 26 +/- 8 beats/min with placebo, P=.006). CONCLUSIONS: Our findings challenge the concept that St John's wort elicits a major change in norepinephrine uptake or monoamine oxidase activity in vivo. The consistent increase in plasma DOPAC concentrations might suggest a novel mode of action or an inhibitory effect on dopamine beta-hydroxylase that should be followed up. We propose that a combination of physiologic and biochemical profiling may help better define the mode of action and potential side effects of herbal remedies.     

Silent autonomic dysreflexia during a routine bowel program in persons with traumatic spinal cord injury: a preliminary study

OBJECTIVE: To determine the existence and frequency of silent autonomic dysreflexia in subjects with a complete spinal cord injury (SCI) above the neurologic level of T6. DESIGN: Prospective design. SETTING: Blood pressure monitoring of subjects during a routine bowel program. PARTICIPANTS: Ten subjects with chronic (>1 y), complete (American Spinal Injury Association Impairment Scale class A) SCI with a neurologic level of injury above T6. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: An increase in systolic blood pressure (SBP) of greater than 20 to 40 mmHg above baseline or an SBP greater than 150 mmHg. RESULTS: The mean resting blood pressure for the subject group was 104/65 mmHg. During the bowel program, no subject reported experiencing any of the classic symptoms of autonomic dysreflexia. The mean maximum blood pressure recorded during the bowel program was 160/90 mmHg. All of the patients had an increase in SBP greater than 20 mmHg above baseline, and 70% had an increase in SBP greater than 40 mmHg above baseline. Sixty percent of subjects had an increase in SBP greater than 150 mmHg, with 40% of subjects reaching an SBP greater than 170 mmHg at least once during their bowel program. CONCLUSION: Silent autonomic dysreflexia occurs frequently in SCI during bowel programs. Further study is recommended to determine whether preventative measures or treatment is needed.     

Effects of graduated compression stockings on cardiovascular and metabolic responses to exercise and exercise recovery in persons with spinal cord injury

OBJECTIVE: To investigate whether reporting blood redistribution by means of graduated elastic stockings affects exercise and postexercise responses in people with spinal cord injury (SCI). DESIGN: Crossover trial. SETTING: Physical medicine and rehabilitation department in France. PARTICIPANTS: Fourteen men with traumatic SCI, grouped according to their level of injury. INTERVENTIONS: Subjects performed 2 maximal wheelchair exercise tests 1 week apart, in random order and under a counter-balanced design. One test was done with and the other without graduated elastic stockings (21 mmHg). MAIN OUTCOME MEASURES: Blood lactate, blood pressure, heart rate, maximal power output, and oxygen consumption (Vo2). RESULTS: Postexercise venous lactate concentration was reduced in SCI subjects with lesion levels below T6 while wearing graduated elastic stockings during both exercise and recovery (10.9+/-3.9 mmol/L vs 12.5+/-4.6 mmol/L, P<.05). There were no significant differences in submaximal and maximal values (heart rate, Vo2, power output) between subjects tested with and without graduated elastic stockings. CONCLUSIONS: Wearing elastic stockings affects postexercise responses by decreasing lactate concentration in well-trained, low-level paraplegic patients after a maximal exercise. The relatively low pressure generated by the stockings may not, however, influence the venous system enough to produce improved performance and cardiovascular responses.     

Wavelet analysis of skin blood oscillations in persons with spinal cord injury and able-bodied subjects

OBJECTIVE: To assess the blood oscillations in the skin over the ischial tuberosity (high-risk area for pressure ulcer) using spectral analysis of laser Doppler flowmetry signals based on wavelet transform. DESIGN: Wavelet analysis of skin blood oscillations in persons with spinal cord injury (SCI) and able-bodied subjects. SETTING: Seating and body support interface laboratory. PARTICIPANTS: Ten men were recruited for this study, of whom 5 were able-bodied subjects (age, 31.2+/-3.3 y) and 5 were persons with SCI (age, 37.2+/-7.3 y). INTERVENTIONS: External pressure of 16.0 kPa (120 mmHg) was applied to the ischial tuberosity via 1 specifically designed pneumatic indentor. The loading duration was 30 minutes. MAIN OUTCOME MEASURES: Skin blood flow was monitored for 10 minutes prior to loading and 20 minutes after the prescribed loading period. With spectral analysis based on wavelet transform, 5 frequency intervals were identified (.01-.02, .02-.06, .06-.15, .15-.40, .40-2.0 Hz) corresponding to endothelial related metabolic, neurogenic, myogenic, respiratory, and cardiac activities, respectively. RESULTS: The relative amplitude of the metabolic component for persons with SCI was significantly lower (F=5.26, P=.032) during the resting conditions as compared with able-bodied subjects. During the postloading period, the response of oscillatory activities was evidently lower in the skin over the ischial tuberosity for persons with SCI when compared with able-bodied subjects. In addition, the relative amplitude of the neurogenic component (.02-.06 Hz) during postloading was significantly lower for persons with SCI (F=5.44, P=.029). CONCLUSIONS: These findings suggest that the contributions of endothelial related metabolic and neurogenic activities to the blood perfusion regulation become relatively less for persons with SCI during the resting and postloading periods, respectively.     

Differential inhibiton of alpha-1 and alpha-2 adrenoceptor-mediated pressor responses in pithed rats

The relative potencies of alpha adrenoceptor antagonists at pre- and postsynaptic receptors were assessed by comparing their effects on increments in plasma norepinephrine levels and blood pressure during stimulation of the sympathetic outflow from the spinal cord of pithed rats. Since increments in blood pressure are related to the logarithms of increases in plasma norepinephrine, the latter appear to reflect levels of the catecholamine at vascular alpha receptors. Phenoxybenzamine, dibenamine and chlorpromazine were found to block preferentially postsynaptic alpha receptors, phentolamine and tolazoline were nearly equipotent at pre- and postsynaptic receptors and mianserin and piperoxan were more potent inhibitors of presynaptic alpha receptors. Phenoxybenzamine and dibenamine were much more effective in blocking the pressor responses to sympathetic stimulation than administered norepinephrine. The opposite was true of mianserin and piperoxan, whereas phentolamine appeared to be about equipotent in blocking the pressor response to stimulation and norepinephrine. These results suggest that the pressor effects of administered norepinephrine is mediated by different receptors (alpha-2-type) than is the pressor response to stimulation of the sympathetic outflow which appears to be mediated by alpha-1-type adrenoceptors.     

Hysteresis of the venous pressure-volume relationship in the forearm of borderline hypertensive subjects.

1. The forearm venous pressure-volume relationship was studied in 14 young men with borderline hypertension and in 16 control subjects of the same age and sex. Strain-gauge plethysmography was used to evaluate volume changes after slow increases and decreases in distention, in order to estimate the amplitude of the hysteresis curve. 2. Compared with normotensive control subjects, subjects with borderline hypertension had significantly higher values of blood pressure, heart rate and forearm blood flow. 3. Baseline forearm venous tone was slightly, but not significantly, increased in borderline hypertensive subjects (21.35 +/- 6.53 versus 18.75 +/- 5.95 mmHg ml-1 100 ml-1) and was significantly enhanced after a cold pressor test. The increase was no higher in the borderline hypertensive subjects than in the normotensive control subjects. 4. The area of the hysteresis curve was significantly decreased (7.58 +/- 3.58 versus 10.34 +/- 5.67 arbitrary units; P = 0.0092) as was the extent of isotonic relaxation (creep) (0.28 +/- 0.11 versus 0.39 +/- 0.22 ml/100 ml; P = 0.0098) in borderline hypertensive subjects compared with control subjects. Both parameters were unaffected by the cold pressor test. 5. The study suggests that the viscous component of the venous wall is altered in young patients with borderline hypertension, indicating intrinsic changes in vascular segments which are not exposed to increased intraluminal pressure.     

Sympathetic activation during the cold pressor test: influence of stimulus area

Summary. The purpose of this study was to determine the effect of the size of the stimulus area on the muscle sympathetic nerve activity (MSNA), systolic arterial blood pressure (SAP), and heart rate responses to the cold pressor test. To accomplish this, these variables were measured before (control), during, and after 1·5 min of ice water immersion of either one or both hands in nine healthy subjects (aged 19–27 years). The cold stimulus elicited significant increases above control levels in all three variables under both conditions (P<0·05). Immersion of both hands produced a much greater increase in total MSNA (+366%) than immersion of a single hand (+187%) (P<0·05). However, the magnitudes of the increases in SAP and heart rate during two-hand immersion (29±6 mmHg and 10±2 beats min^-1) were not significantly different from the responses during the one-hand trials (24±5 mmHg and 6±2 beats min^-1, P>0·05). There was a strong, direct relationship between total MSNA and SAP responses during one-hand immersion (r= 0·93, P<0·001) but not during immersion of both hands (r= 0·66, P= 0·08). These findings indicate that during the cold pressor test the magnitude of the increase in sympathetic discharge to skeletal muscle, but not the systolic blood pressure response, is influenced by the size of the tissue area exposed to the stimulus.     

Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man.

To determine the plasma epinephrine thresholds for its metabolic and hemodynamic actions and plasma epinephrine metabolic clearance rates, 60-min intravenous epinephrine infusions at nominal rates of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min were performed in each of six normal human subjects. These 30 infusions resulted in steady-state plasma epinephrine concentrations ranging from 24 to 1,020 pg/ml. Plasma epinephrine thresholds were 50-100 pg/ml for increments in heart rate, 75-125 pg/ml for increments in blood glycerol and systolic blood pressure, 150-200 pg/ml for increments in plasma glucose (the resultant of increments in glucose production and decrements in glucose clearance), blood lactate, blood beta-hydroxybutyrate, and diastolic blood pressure, and greater than 400 pg/ml for early decrements in plasma insulin. Changes in blood alanine, plasma glucagon, plasma growth hormone, and plasma cortisol were not detected. At steady-state plasma epinephrine concentrations of 24-74 pg/ml, values overlapping the basal normal range, the mean (+/-SE) plasma metabolic clearance rate of epinephrine was 52 +/- 4 ml x min-1 x kg-1; this value rose to 89 +/- 6 ml x min-1 x kg-1 (P less than 0.01) at steady-state epinephrine concentrations of 90-1,020 pg/ml. We conclude that in human subjects: (a) the plasma epinephrine thresholds for its hemodynamic and metabolic actions lie within the physiologic range, (b) epinephrine and norepinephrine accelerate their own metabolic clearance, and (c) epinephrine is 10 times more potent than norepinephrine.     

Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. Studies in lean and obese men.

To explore the interactions between insulin action and norepinephrine (NE) on blood pressure and muscle vascular resistance, we studied seven lean (66 +/- 1 kg) sensitive and seven age-matched obese (96 +/- 3 kg) insulin-resistant men after an overnight fast. Both groups were normotensive; however, the obese exhibited higher basal blood pressure, 90.8 +/- 2.2 vs. 83.4 +/- 1.6 mmHg, P < 0.04. Each subject was studied on two separate days during either saline (S) infusion or a euglycemic hyperinsulinemic clamp (I) achieving insulin concentrations of approximately 70 microU/ml. After 180 min of either S or I, NE was infused systemically at rates of approximately 50, 75, and 100 pg/kg per min. Glucose uptake was measured in whole body ([3-3H]glucose) and in leg by the balance technique. The results indicate: (a) the NE/pressor dose-response curve was decreased (shifted to the right) during I in lean but not in obese subjects, (b) I enhanced NE metabolic clearance by 20% in lean but not in obese, (c) NE decreases leg vascular resistance more in lean than in obese, and (d) NE causes a approximately 20% increase in insulin-mediated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE pressor sensitivity and decreased NE metabolic clearance. Both of these mechanisms can potentially contribute to the higher incidence of hypertension in obese man. Insulin resistance is likely to be a predisposing but not sufficient factor in the pathogenesis of hypertension. Because the obese group exhibited higher basal blood pressure, it is possible that our results reflect this difference. Further studies will be required to clarify this issue.     

Use of alpha 2 adrenoreceptor agonists and antagonists in the functional assessment of the sympathetic nervous system.

We studied the effects of clonidine, an alpha 2-adrenoreceptor agonist, and yohimbine, an alpha 2-adrenoreceptor antagonist, on blood pressure, heart rate, and plasma catecholamines in 12 patients with autonomic dysfunction. Clonidine (0.1 mg, orally) lowered blood pressure 18 +/- 3 torr in six subjects and raised it 5 +/- 1 torr in six. The change in blood pressure in response to this dose of clonidine was inversely proportional to the supine level of norepinephrine (P less than 0.05). Yohimbine (4-64 micrograms/kg) raised plasma norepinephrine and blood pressure in six patients with degenerative autonomic dysfunction. Yohimbine also attenuated by 50% (P less than 0.05) the hypotensive response to head-up tilt of patients with degenerative autonomic dysfunction. Clonidine depends upon postjunctional hypersensitivity and the degree of autonomic insufficiency to elicit its pressor response. In contrast, the pressor response to yohimbine is related to the capacity of the sympathetic nervous system to be activated and release norepinephrine. If plasma norepinephrine levels following yohimbine administration are monitored, the biochemical and hemodynamic response to the drug may provide a sensitive indication of the capacity of the sympathetic nervous system to be activated in patients with autonomic dysfunction.     

Fluoxetine-induced pressor response in freely moving rats: a role for vasopressin and sympathetic tone

The present study was performed in order to assess, in freely moving rats, the cardiovascular effects of central administration of fluoxetine, a serotonin reuptake inhibitor. Two kinds of experiments were performed: 1) acute central administration of fluoxetine. and 2) chronic intraperitoneal administration of fluoxetine plus selegiline, a monoamine oxidase B inhibitor. Intracerebroventricular (i.c.v.) administration of fluoxetine (5-50 microg) induced an increase in blood pressure. This fluoxetine-induced pressor response reached its maximal 1 hour after injection without any significant change in heart rate. At the dose of 10 microg i.c.v., fluoxetine significantly increased mean blood pressure by 16 +/- 4 mmHg. This pressor response was reduced by an intravenous (i.v.) pretreatment with the alpha1-adrenoceptor antagonist, prazosin (500 microg kg(-1)) (+ 7 +/- 4 mmHg, P <0.05) or with the V1A-vasopressin receptor antagonist (20 microg kg(-1)) (+5 +/- 3 mmHg, P < 0.05). The pressor response was completely abolished by a concomitant pretreatment with prazosin plus the V1A-vasopressin receptor antagonist. Pretreatment with the beta-adrenoceptor antagonist, propranolol (1 mg kg(-1) i.v.), or the 5-HT2 receptor antagonist, ketanserine (5 mg kg(-1) i.v.), did not modify the fluoxetine-induced pressor response. In freely moving rats receiving fluoxetine (10 microg i.c.v.), vasopressin plasma levels were significantly higher (39 +/- 5 pg mL(-1) than in rats receiving 10 microL i.c.v. saline (14 +/- 4 pg mL(-1)). A 30 day intraperitoneal (i.p.) administration of fluoxetine in association with selegiline induced an increase in noradrenaline plasma levels and locomotor activity without any significant change in blood pressure and heart rate. These data suggest that, the pressor response elicited by central acute administration of fluoxetine is mediated by both an increase in sympathetic tone and vasopressin release. This observation could suggest the putative interest of alpha1-adrenoceptor and or V1A-vasopressin receptor antagonists in the treatment of "Serotonin Syndrome".     

Reduced baroreflex sensitivity in elderly humans is not due to efferent autonomic dysfunction

A progressive decline in baroreflex sensitivity (BRS) is a characteristic feature of human aging, the basis of which is poorly understood. The purpose of the present study was to determine whether alterations in efferent baroreflex function might contribute to the age-related decrease in BRS. We studied 10 healthy young (mean age 30.5 years; age range 22-40 years; six male) and 10 healthy elderly (mean age 70.7 years; age range 67-75 years; five male) volunteers. We tested efferent cardiac vagal function using the bradycardiac response to the cold face test, and efferent sympathetic function using heart rate and blood pressure responses to four stress tests: (i) low-level cognitive stress, (ii) high-level cognitive stress, (iii) hand immersion in ice water (cold pressor test) and (iv) isometric sustained hand-grip. Haemodynamic responses to these stresses are mediated via efferent baroreflex pathways, whereas the afferent components of each reflex response are independent of afferent baroreflex pathways. BRS was measured from simultaneous Finapres-derived continuous blood pressure and digital ECG R-R interval data using the sequence analysis paradigm. As expected, BRS was significantly reduced in the elderly group (7. 29+/-0.74 ms/mmHg; mean+/-S.E.M.) compared with the young group (13. 84+/-1.13 ms/mmHg; P<0.001). However, neither the bradycardiac responses to the cold face test nor the efferent sympathetically mediated heart rate/blood pressure responses to the stress test battery were significantly different between the young and elderly groups. We conclude that the age-related decrease in BRS is not attributable to impairments in the efferent sympathetic or parasympathetic system components of the baroreceptor reflex pathway.     

Cardiovascular effects of verapamil in essential hypertension

Calcium antagonists may affect the regulation of body sodium and adrenergic-dependent mechanisms. Exchangeable sodium, blood volume, plasma norepinephrine, renin, aldosterone, pressor responsiveness to norepinephrine, heart rate responses to isoproterenol, and lipid metabolism were studied in 15 patients with essential hypertension after 8 weeks of treatment with verapamil (348 +/- 68 (SD) mg/day). Supine blood pressure decreased from 153/103 +/- 19/12 mm Hg to 140/95 +/- 14/12 mm Hg (P less than 0.01). Exchangeable sodium, blood volume, plasma norepinephrine, renin and aldosterone, serum total cholesterol, the lipoprotein fractions, and apoprotein levels were unchanged. The norepinephrine pressor and the isoproterenol chronotropic doses tended to increase, whereas the dose-response curve of blood pressure related to plasma norepinephrine was significantly displaced to the right (F = 5.34; P less than 0.05). The antihypertensive effect of verapamil is associated with a decreased cardiovascular pressor responsiveness to norepinephrine without changes in endogenous noradrenergic activity. Moreover, verapamil does not modify the sodium/fluid volume state, the activity of the renin-angiotensin aldosterone axis, or lipid metabolism.