Hemodynamic reactivity to sympathoadrenal stimulation in adrenalectomized women

To determine the extent to which circulating epinephrine (E) mediates the cardiovascular effects of sympathoadrenal stimulation, we studied the blood pressure (BP), heart rate, forearm vascular resistance, and plasma catecholamine responses to a mental arithmetic test, head-up tilt test, and cold pressor test in 10 adrenalectomized women and 10 age-matched normotensive women. The mean basal diastolic BP was slightly higher in the adrenalectomized women (80 vs. 68 mm Hg; P less than 0.05). During mental arithmetic, the adrenalectomized women had a smaller heart rate increase than the normal women [6 +/- 1% (+/- SE) vs. 16 +/- 4%; P less than 0.05], but the BP response was not different. During the head-up tilt and cold pressor tests the hemodynamic responses were similar in the adrenalectomized and normal women. As expected, plasma E was undetectable in the adrenalectomized women. Plasma norepinephrine (NE) did not change in either group during mental arithmetic. In the adrenalectomized women the plasma NE increases during the head-up tilt and cold pressor test were not significantly different from those in the normal women. Thus, the adrenalectomized women had a normal pressor response during all 3 types of adrenergic stimulation, apparently independent of plasma E. Together with the normal plasma NE responses to head-up tilt and cold exposure, we challenge the contention that the E-mediated presynaptic beta-adrenergic stimulation of NE release plays a pivotal physiological role during short term adrenergic stress.     

Effects of nifedipine on baroreflex modulation of vascular resistance in man

Studies in animals have demonstrated that, in addition to their vascular effects, calcium channel blockers have important effects on baroreceptor function. We performed a series of experiments to determine if nifedipine, in doses employed clinically, alters baroreflex control of vascular resistance in normal humans. Forearm vasoconstrictor responses of 14 normal subjects to unloading of baroreceptors with lower body negative pressure (LBNP), to a cold pressor test and during intra-arterial infusions of norepinephrine were studied in the control state and following administration of nifedipine. Nifedipine had no effect on baseline mean arterial pressure or central venous pressure. Heart rate and forearm blood flow (FBF) increased significantly following nifedipine: heart rate = 59.7 +/- 2.4 bpm before and 72.6 +/- 4.4 bpm after nifedipine (mean +/- SE, p less than 0.001, n = 14); FBF = 4.6 +/- 0.4 ml X min-1 X 100 ml-1 before and 6.7 +/- 1.0 ml X min1 X 100 ml-1 after nifedipine (p less than 0.02, n = 14). Forearm vascular resistance (FVR) tended to decrease following nifedipine but the difference was not significant: FVR = 21.1 +/- 1.4 units before and 17.8 +/- 2.3 units after nifedipine (p = 0.07, n = 14). Nifedipine attenuated forearm vasoconstrictor responses to cold pressor stimulus: delta FVR during cold pressor test = +10.3 +/- 2.4 units before and +4.7 +/- 1.4 units after nifedipine (p less than 0.02, n = 14). Likewise, nifedipine depressed vasoconstrictor responses to intra-arterial infusion of norepinephrine: delta FVR during norepinephrine = +15.5 +/- 3.4 units before and +10.2 +/- 2.9 units after nifedipine (p less than 0.05, n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic peptide attenuates the reflex sympathetic responses to lower body negative pressure

The authors studied the effect of intravenous infusion of atrial natriuretic peptide (ANP) on the plasma catecholamine and forearm vasoconstrictor responses to cardiopulmonary baroreflex deactivation in six normal, male volunteers in order to determine whether ANP influences reflex forearm vasoconstriction in humans. Unloading of low-pressure cardiopulmonary baroreceptors (CPBR) was accomplished by application of low levels (-10 and -20 mm Hg) of lower body negative pressure (LBNP). The authors measured the plasma norepinephrine (NE) and epinephrine, the mean arterial pressure (MAP), and the forearm vascular resistance (FVR) responses to reflex sympathetic activation by LBNP. ANP infusion (0.1 microgram.kg-1.min-1) decreased (p less than 0.01) basal MAP, as well as plasma renin activity and plasma aldosterone levels (p less than 0.05). ANP infusion also reduced (p less than 0.01) plasma NE responses to both levels of LBNP and tended to decrease both epinephrine and FVR during ANP infusion at -20 mm Hg LBNP (p = 0.8). These data suggest that exogenous ANP inhibits the reflex sympathetic responses that occur with CPBR unloading. The blunted plasma NE responses to CPBR unloading parallel the attenuation of FVR response to LBNP during ANP infusion, despite significant LBNP-induced hypotension.     

Effects of diltiazem on hormonal and hemodynamic responses to lower body negative pressure and tilt in patients with mild to moderate systemic hypertension

Mean arterial blood pressure, forearm vascular resistance, plasma norepinephrine, plasma renin activity and aldosterone responses to graded lower body negative pressure and tilt at 80 degrees were examined in 10 men with mild to moderate essential hypertension before and after 12 weeks of diltiazem (240 to 360 mg/day) therapy. Diltiazem therapy lowered basal supine systolic and diastolic blood pressures without affecting basal heart rate. Mean arterial blood pressure and forearm vascular resistance were decreased from 114 +/- 1.5 to 105 +/- 1 mm Hg, p less than 0.01 and from 29.3 +/- 3.5 to 18.9 +/- 2.1 units, p less than 0.01, respectively. Diltiazem therapy had no effect on basal supine levels of norepinephrine, plasma renin activity or aldosterone, nor on the responses of these hormones to lower body negative pressure. Diltiazem did decrease the forearm vascular resistance responses to lower body negative pressure and tilt. Diltiazem abolished an orthostatic increase (10 +/- 0.3 mm Hg) in mean arterial blood pressure and this was associated with a greater plasma norepinephrine response to tilt. These results suggest that diltiazem decreases vascular resistance through a reduction in the postjunctional effects of norepinephrine on vascular smooth muscle.     

Effect of advancing age on cardiopulmonary baroreceptor function in hypertensive men

Blood pressure, heart rate, forearm vascular resistance, and hormonal responses to graded lower body negative pressure were investigated in 15 hypertensive men younger than 55 years of age (mean age, 44 +/- 2 years) and 13 comparably hypertensive men older than 55 years of age (mean age, 63 +/- 2 years). Baseline forearm vascular resistance was greater in the elderly group compared with the younger hypertensive men. However, forearm vascular resistance responses to selective unloading of low pressure cardiopulmonary baroreceptors were similar in the two groups. This finding suggests that normal vascular responses to the unloading of cardiopulmonary baroreceptors are preserved in subjects with advancing age and mild to moderate hypertension. Baseline plasma norepinephrine levels, as well as norepinephrine responses to lower body negative pressure, were comparable in the two groups. This finding suggests that, unlike normotensive subjects, essential hypertensive subjects do not have an age-related increase in sympathetic nervous system activity.     

Neurohumoral and hemodynamic effects of lower body negative pressure in patients with congestive heart failure

Baroreflex modulation of forearm vascular resistance (FVR) has been reported to be abnormal in patients with congestive heart failure (CHF). However, the neurohumoral mechanisms for this impairment are not defined. We assessed the responses of arterial pressure, FVR, plasma norepinephrine, and plasma renin activity to lower body negative pressure in 29 patients with compensated CHF (New York Heart Association class III and IV) and in 11 normal age-matched control subjects. Baseline mean arterial pressure (83 +/- 2 vs 84 +/- 2 mm Hg) and mean arterial pressure during LBNP (-10, -20, and -40 mm Hg) were not significantly different in the two groups. Basal FVR (43.7 +/- 4 vs 27 +/- 2 units), plasma norepinephrine (605 +/- 81 vs 155 +/- 8 pg/ml), and plasma renin activity (8.3 +/- 1.7 vs 1.2 +/- 0.2 ng/ml/hr) were significantly (p less than 0.01) higher in patients with CHF. The relative increases in FVR responses during LBNP of -10, -20, and -40 mm Hg (10 +/- 4% vs 70 +/- 12%, 17 +/- 6% vs 106 +/- 21%, and 24 +/- 9% vs 152 +/- 28%) were markedly attenuated in patients with CHF compared to control subjects. Plasma norepinephrine and plasma renin activity responses during LBNP were also attenuated in patients with heart failure. Our results suggest that baroreflex control of FVR and plasma norepinephrine and plasma renin activity is impaired in CHF because of the inability of the cardiopulmonary baroreceptors to alter sympathetic outflow.     

Parallel renal and extremity blood supply abnormalities in nonmodulation: responses to ACE inhibition

The aim of this work was to ascertain, in nonmodulating essential hypertension, whether the abnormality in the renal blood supply is extended to the extremities and showed a similar response to ACE inhibition and whether these abnormalities could be identified in normotensive offspring of hypertensives, as non-modulation is a familial process with genetic underpinnings. We measured forearm vascular blood flow (FBF) and forearm vascular resistance (FVR) by plethysmography and urinary albumin excretion in 20 normotensive without family story of hypertension (NT: 25+/-9 years), 10 modulating offspring of hypertensive parents (MHO: 25+/-6 years), 10 nonmodulating offspring of hypertensive parents (NMHO: 26+/-5 years), 12 modulating essential hypertensives (MHT: 34+/-5 years), and 11 nonmodulating essential hypertensives (NMHT: 32+/-4 years). Measurements were repeated in hypertensives after 3-month treatment with ramipril (5 mg daily). Nonmodulating individuals showed lower maximum FBF (NMHT: 41.96+/-3.3 mL/100 g per minute and NMHO: 35.6+/-9.0 mL/100 g per minute) than modulating subjects (MHT: 57.5+/-10.0 mL/100 g per minute and MHO: 51.8+/-7.0 mL/100 g per minute; P<0.003). Likewise, all nonmodulating subjects showed higher minimum FVR (NMHT: 2.5+/-0.2 AU; NMO: 2.8+/-0.5 AU) than modulating individuals (MHT: 1.9+/-0.5 AU; MHO, 1.8+/-0.3AU; P<0.025). Urinary albumin excretion was higher in NMHT and NMHO than MHT, MHO, and NT (P<0.05). Ramipril increased maximum FBF to 53.8+/-8.0 mL/100 g per minute and reduced minimum FVR to 1.9+/-0.5 AU in NMHT (P<0.01). Likewise, ramipril increased effective renal plasma flow and reduced renal vascular resistance and urinary albumin excretion only in NMHT (P<0.05). These results have shown an early involvement of the peripheral circulation in association with increased urinary albumin excretion not only in essential hypertensives but also in NMHO. The effectiveness of ramipril in reducing minimum FVR and urinary albumin excretion in NMHT also suggests a common mechanism.     

Increased plasma and cerebrospinal fluid norepinephrine in older men: differential suppression by clonidine

To evaluate the effect of advanced age on central nervous system noradrenergic activity, cerebrospinal fluid (CSF) and plasma norepinephrine (NE) concentrations were measured concurrently in 14 older [mean, 65 +/- 9 (+/- SD) yr] and 33 younger (25 +/- 2 yr) normal men. CSF NE was significantly higher in older men than in young men [214 +/- 75 (+/- SD) vs. 164 +/- 56 pg/mL (1.26 +/- 0.44 vs. 0.97 +/- 0.33 nmol/L); P less than 0.02] as was plasma NE [282 +/- 103 vs. 211 +/- 63 pg/mL (1.67 +/- 0.61 vs. 1.25 +/- 0.37 nmol/L); P less than 0.02]. Subgroups of young and older men underwent two lumbar punctures, one of which was performed 100 min after the administration of 5 micrograms/kg oral clonidine. The young (n = 7) and older (n = 7) men had similar plasma clonidine levels [1.0 +/- 0.1 vs. 0.8 +/- 0.1 ng/mL (4.35 +/- 0.43 vs. 3.48 +/- 0.78 nmol/L)] and CSF clonidine levels [0.18 +/- 0.02 vs. 0.22 +/- 0.03 ng/mL (0.78 +/- 0.09 vs. 0.96 +/- 0.13 nmol/L)]. The suppression of CSF NE by clonidine was significantly greater (P less than 0.015) in young men [189 +/- 44 to 104 +/- 26 pg/mL (1.12 +/- 0.26 to 0.62 +/- 0.15 nmol/L)] than in older men [190 +/- 49 to 164 +/- 58 pg/mL (1.12 +/- 0.29 to 0.97 +/- 0.34 nmol/L)]. In contrast, the suppression of plasma NE by clonidine did not significantly differ between young [242 +/- 72 to 93 +/- 24 pg/mL (1.43 +/- 0.43 to 0.55 +/- 0.14)] and older men [285 +/- 102 to 167 +/- 84 pg/mL (1.68 +/- 0.60 to 0.99 +/- 0.50 nmol/L)]. These data suggest that decreased sensitivity of alpha 2-adrenergic mechanisms regulating CNS noradrenergic activity may contribute to increased CNS noradrenergic activity with aging.     

Increased ratio between changes in blood pressure and plasma norepinephrine in essential hypertension.

The pathogenic role of the sympathetic system in essential hypertension was evaluated by combined analysis of plasma catecholamine levels and the pressor sensitivity to endogenous norepinephrine. The latter was estimated indirectly by the ratio between changes in blood pressure and those in plasma norepinephrine after adrenergic neuronal blockage with debrisoquine (given orally for 6 weeks). Normal subjects and patients with borderline or established essential hypertension had comparable pretreatment levels of plasma norepinephrine and epinephrine. Debrisoquine lowered plasma norepinephrine by a similar degree (almost 50%) in these three groups; in contrast, blood pressure decreased only slightly in normal or borderline hypertensive subjects [-3.4 +/- 3.2% and -5.4 +/- 1.6% (SE), respectively] but fell significantly more (P less than 0.005) in patients with established essential hypertension (-20.7 +/- 3.9%). The ratio between percentile changes in blood pressure and those in endogenous norepinephrine levels was comparable in normal and borderline hypertensive subjects (0.03 +/- 0.08 and 0.17 +/- 0.04, respectively), but increased (P less than 0.001) in established essential hypertension (0.62 +/- 0.11). This suggests that essential hypertension may be maintained, at least partly, by the inappropriate association of normal plasma norepinephrine levels with increased norepinephrine pressor sensitivity.     

Vascular structure enhances regional resistance responses in mild essential hypertension

Forearm blood flow (FABF) and forearm vascular resistance (FAVR) responses to sequential regional infusions of norepinephrine (NE) and angiotensin II (Ang II) were examined in 24 hypertensive and 18 matched normotensive subjects. Sensitivity to both vasoconstrictors, defined as the percentage increase in FAVR in response to the lowest dose of each agonist, was similar in the two groups. Also, the FABF response curve to the full range of both agonists did not differ between hypertensives and normotensives by analysis of variance (ANOVA). While the FAVR responses at the lowest doses of both NE and Ang II were similar in hypertensives and normotensives, FAVR responses in hypertensives diverged progressively from the normotensive response pattern, P less than 0.01 according to ANOVA. The hypertensives achieved greater maximum FAVR levels at the highest doses of both agonists, P less than 0.05 according to repeated measures ANOVA. After 10 min of ischaemic exercise, FAVR was higher in hypertensives than in normotensives (2.24 +/- 0.10 versus 1.87 +/- 0.08; P = 0.02, respectively). This value for FAVR was termed the minimum FAVR (mFAVR). The overall response pattern characterized by increased mFAVR, unchanged threshold sensitivity, steeper slope, greater maximum response and similarity of responses to both NE and Ang II is most consistent with a structural augmentation of resistance responses. A model was used in an effort to increase understanding of the vessel morphology. This model suggested that an increased wall/lumen ratio, perhaps without an actual increase in vascular smooth muscle mass, played an important role in the observed FAVR pattern.     

Attenuation of reflex forearm vasoconstriction by alpha-human atrial natriuretic peptide in men

This study examined whether atrial natriuretic peptide (ANP) modulates reflex forearm vasoconstriction in humans. Synthetic alpha-human ANP (alpha-hANP) was infused at a rate of 0.03 microgram/kg/min in 8 healthy men (mean age 23 +/- 0.7 years, mean +/- SEM). The alpha-hANP decreased systolic blood pressure and central venous pressure (CVP) but did not significantly alter resting heart rate and forearm vascular resistance (FVR). The magnitudes of reflex increases in FVR during lower body negative pressure (LBNP) at -110, -20, and -40 mm Hg were less during infusion of alpha-ANP than those magnitudes during infusion of saline solution. The slope of the regression line relating changes in CVP and those in FVR was less during infusion of alpha-hANP than the slope during infusion of saline solution. Forearm vascular responses to intra-arterial infusion of norepinephrine at doses of 100, 200, and 500 ng/min did not significantly differ during infusion of alpha-hANP and saline solution. These results suggest that alpha-hANP attenuates cardiopulmonary baroreflex control of FVR in normal men.     

Elevated insulin, norepinephrine, and neuropeptide Y in hypertension

To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose. Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives. Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives. Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77). Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036). We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels.     

Sodium-sensitive hypertension is not associated with higher sympathetic nervous system activity in older hypertensive humans

The majority of older hypertensive humans are sodium sensitive and they are characterized by increased alpha-adrenergic responsiveness relative to their level of sympathetic nervous system (SNS) activity. To test the hypothesis that heightened SNS activity and/or increased alpha-adrenergic receptor responsiveness during sodium loading may play a role in the sodium-dependent increase in blood pressure in older sodium-sensitive hypertensives, we used compartmental analysis of [3H]norepinephrine (NE) kinetics to determine the release rate of NE into an extravascular compartment (NE2) as an index of systemic SNS activity and determined forearm blood flow responses to graded intrabrachial artery NE and angiotensin II (ANG II) infusions and platelet membrane alpha2-receptor properties in 24 older (age 64 +/- 7 years) hypertensive subjects. Subjects were studied at the end of 1 week of a low (20 mmol/day)- and again at the end of 1 week of a high (200 mmol/day)-sodium diet. Subjects were categorized as sodium sensitive (SS) if they had a > or = 5 mm Hg increase in mean arterial blood pressure (MABP) with dietary sodium loading (n = 16), or sodium-resistant (SR) if their MABP increased by < 5 mm Hg (n = 8). Neither dietary sodium intake nor sodium-sensitivity status significantly affected arterial plasma NE levels, NE2, or other NE kinetic parameters. Forearm blood flow responses to NE or to ANG II, and platelet alpha2-receptor properties were similar between the SS and SR groups. These results suggest that the sodium-dependent increase in MABP that characterizes SS hypertension among older humans is not because of an increase in systemic SNS activity or increased arterial adrenergic receptor responsiveness.     

Antihypertensive contribution of sodium depletion and the sympathetic axis during chronic angiotensin II converting enzyme inhibition

The known physiological adaptation of cardiovascular sensitivity to variations in angiotensin II (Ang II) levels would predict that the blood pressure (BP)-lowering effect of Ang II inhibition might be at least partly counterbalanced by enhanced Ang II reactivity. Therefore, factors other than Ang II inhibition per se may contribute to the antihypertensive mechanisms of angiotensin converting enzyme (ACE) inhibitors. In order to further investigate this, the body sodium-blood volume state as well as the pressor reactivity to infused Ang II or norepinephrine (NE) were assessed in 12 normal subjects and 16 patients with essential hypertension given a placebo, and after 6 weeks of intervention with enalapril (20-40 mg/day). Enalapril produced in both groups similar falls in plasma ACE activity (P less than 0.0001) and upright plasma aldosterone (P less than 0.01), and a rise in plasma renin activity (PRA; P less than 0.05). BP decreased from 156/107 +/- 3/2 (mean +/- s.e.m.) to 142/94 +/- 5/3 mmHg (P less than 0.001) in the hypertensives and from 118/84 +/- 4/2 to 111/73 +/- 4/3 mmHg (P less than 0.01) in the normal subjects. In the hypertensive patients only, the Ang II pressor reactivity relative to Ang II plasma levels during Ang II infusion was increased (P less than 0.01), while the NE pressor reactivity relative to NE plasma levels during NE infusion (P less than 0.01) as well as the exchangeable body sodium (-5%, P less than 0.001) were reduced significantly. Blood and plasma volume, levels of plasma atrial natriuretic factor and catecholamines, and the heart rate and its response to isoproterenol were unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age differences in plasma norepinephrine kinetics in humans

To determine if the increased plasma norepinephrine (NE) of older individuals is due to greater plasma NE appearance rate and/or decreased NE clearance, arterialized plasma NE kinetics were measured in 25 healthy young (27 +/- 6 yr, M +/- SD) and 18 healthy older volunteers (68 +/- 5 yr) using a tritium-labeled NE isotope dilution technique. Basal NE levels were 54% greater in the older participants (282 +/- 24 vs. 183 +/- 11 pg/ml, M +/- SEM, p less than .001). The mean plasma NE appearance rate was 32% higher (0.33 +/- 0.03 vs. 0.25 +/- 0.02 microgram/m2/min, p less than .016) and NE clearance was 19% lower (1.21 +/- 0.08 vs. 1.49 +/- 0.06 L/min/m2, p less than .006) in the older participants. There was a close correlation between NE appearance rate and NE levels (r = .76, p less than .001, N = 43), but only modest inverse correlation between NE clearance and NE levels (r = -.37, p less than .01, N = 43). Stepwise multiple linear regression analysis revealed that NE appearance rate and clearance explained 80% of the variance in NE levels and that 57% of the variance was attributable to NE appearance, F (1,41) = 54.8, p less than .001, compared with only 14% by NE clearance, F (1, 41) = 6.5, p = .01. We conclude that the principal factor accounting for the higher plasma NE levels of older individuals is an increase in plasma NE appearance rate.     

Effect of a pressor infusion of angiotensin II on sympathetic activity and heart rate in normal humans

We tested the hypothesis that pressor infusions of angiotensin II (AII) could stimulate the sympathetic nervous system as reflected by norepinephrine (NE) spillover in humans. AII was infused at 5 ng/kg/min in six healthy volunteers, with vehicle and phenylephrine infusions as controls, on 3 separate days. Heart rate, mean arterial pressure, plasma NE, NE clearance, and NE spillover were assessed before and after 30-minute infusions of AII, vehicle, or phenylephrine in the supine position and then after 15 minutes of head-up and 15 minutes of head-down tilt. Both AII and phenylephrine raised mean arterial pressure (88 +/- 9.6 to 103 +/- 14 mm Hg, p less than 0.001, and 91 +/- 7.6 to 104 +/- 9.2 mm Hg, p less than 0.001, respectively), whereas heart rate fell only with phenylephrine (60 +/- 6 to 51 +/- 6.3 beats/min, p less than 0.001). Neither plasma NE nor NE spillover was affected by either infusion, and NE clearance declined slightly with both. No changes occurred in any variable during vehicle infusions in the supine position. During upright tilt, NE spillover increases were attenuated by both AII and phenylephrine while NE clearance changes were slightly greater, leaving plasma NE increases similar on each day. During head-down tilt, NE and NE spillover declined comparably on each study day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age and alpha-2 adrenergic regulation of plasma norepinephrine kinetics in humans

To investigate whether the age-related elevation of plasma norepinephrine (NE) is due to impaired alpha-2 adrenergic inhibition of sympathetic nervous system (SNS) outflow, arterialized plasma NE kinetics were measured before and 120 to 140 min after 1.5 and 5.0 micrograms m/kg oral clonidine in 6 old (57 to 78 years) and 8 young (25 to 39 years) normotensive male volunteers. Baseline plasma NE levels were higher in old compared with young men (M +/- SEM, 355 +/- 58 vs. 197 +/- 22 pg/ml, p less than .02). Clonidine produced significant (p less than .05) dose-related reductions in plasma NE, NE appearance rate, NE clearance, and mean arterial blood pressure (MAP) in both groups. There was no difference between old and young men in response to low dose clonidine. Following the higher dose, both groups had similar suppression of plasma NE (-51 +/- 7% vs. -58 +/- 2%, p greater than .05) and NE appearance (-60 +/- 6% vs. -62 +/- 2%, p greater than .05), but older men had a greater fall in NE clearance (-20 +/- 2% vs. -10 +/- 1%, p less than .003) and MAP (-28 +/- 3% vs. -10 +/- 4%, p less than .006). These findings suggest that sensitivity to alpha-2 receptor-mediated suppression of plasma NE and NE appearance is not diminished in elderly men.     

Impairment of cardiopulmonary baroreflex after cardiac transplantation in humans

There is ample evidence for efferent cardiac denervation in patients after cardiac transplantation. However, little is known regarding the effects of the cardiac deafferentation that also results. We examined responses to graded lower-body negative pressure and thus cardiopulmonary baroreceptor unloading in 23 patients 3 to 12 months after cardiac transplantation and compared their responses with those of nine normal subjects. Responses of mean arterial pressure, forearm vascular resistance, and plasma norepinephrine were assessed during lower-body negative pressure and the cold pressor test. Reflex increases in forearm vascular resistance (1.5 +/- 1, 5.0 +/- 1.4, and 6.4 +/- 2.1 vs 14.5 +/- 4.5, 20.3 +/- 6.5, and 34 +/- 11 units) and plasma norepinephrine (42 +/- 12, 58 +/- 15, and 62 +/- 13 vs 49 +/- 14, 94 +/- 25, and 173 +/- 36 pg/ml) during lower-body negative pressure (at -10, -20, and -40 mm Hg) were strikingly smaller in cardiac transplant patients than in normal subjects. The impaired responses of the cardiac transplant patients were not the result of a nonspecific depression of cardiovascular reflexes, since increases in mean arterial pressure (12 +/- 3 vs 10 +/- 2 mm Hg), forearm vascular resistance (19.5 +/- 3.4 vs 18 +/- 5.8 units), and plasma norepinephrine (56 +/- 8 vs 42 +/- 11 pg/ml) during cold pressor test were not significantly different in the two groups. Furthermore, the impaired responses were not caused by the immunosuppressive agents used to treat the cardiac transplant patients, since patients with renal transplants on similar regimens had augmented forearm vasoconstrictor responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased platelet and vascular smooth muscle reactivity to low-dose adrenaline infusion in mild essential hypertension

During low-dose adrenaline infusion, platelet count, platelet size, plasma beta-thromboglobulin (BTG) and forearm vascular resistance (FVR) were measured in twelve 40-year-old men with mild, untreated hypertension. The average platelet count increased from 195 to 226 X 10(9)/l (P less than 0.001), platelet size from 7.31 to 7.53 X 10(-15)/l (P less than 0.01), BTG from 0.61 to 1.08 nmol/l (P less than 0.02) and FVR decreased from 97 to 58 (arbitrary units; P less than 0.001) during the infusion. The change in platelet count reflects splenic release of platelets, the change in plasma BTG reflects platelet release reaction, while the reduced FVR reflects vascular smooth muscle cell relaxation. In 11 normotensive men aged 40 years, platelet count increased from 187 to 201 X 10 g/l (P less than 0.01) during an equal low-dose adrenaline infusion. This increase in platelet count is significantly less than in the hypertensive group (P less than 0.01). There was statistically no significant change in platelet size, BTG or FVR in the normotensive group. Arterial adrenaline rose from 0.5 to 2.5 nmol/l in the hypertensive and from 0.5 to 2.4 nmol/l in the normotensive group. A third group of 12 normotensive men received saline infusion: neither platelet parameters nor FVR changed in this group. Thus, a small and equal dose of adrenaline elicited a greater increase in platelet count, an enhanced platelet release reaction and a more pronounced forearm vasodilation in hypertensive than in normotensive subjects.     

Disparate effects of mental stress on plasma noradrenaline in young normotensive and hypertensive subjects

The response of blood pressure, heart rate and plasma catecholamines to a mental arithmetic and a cold pressor test was studied in 70 patients with mild essential hypertension and in 41 age- and sex-matched normotensives. Each group consisted of three prospectively stratified age classes: 20-29, 30-39 and 40-55 years. During mental arithmetic, hypertensives showed only a higher increment of systolic blood pressure (+17-19%) than normotensives (+12-15%). Plasma noradrenaline in the youngest normotensives (20-29 years) showed a small but significant decrease (-0.20 +/- 0.07 nmol/l) whereas the youngest hypertensives showed a small but significant increase of plasma noradrenaline (+0.14 +/- 0.04 nmol/l). The difference between both groups was highly significant (P less than 0.001). In the two older age classes there was no difference in plasma noradrenaline response between normo- and hypertensives. During the cold pressor test both the cardiovascular and plasma noradrenaline response were of the same magnitude in normo- and hypertensives. These data reinforce the concept that the increased sympathetic reactivity to mental stress in hypertensives may be restricted to the younger age.