Changes In Plasma Norepinephrine Research Articles

Role of vasopressin in cardiovascular and neurohormonal responses to intracerebroventricular hypertonic NaCl.

To determine the significance of vasopressin in cardiovascular and neurohormonal responses caused by centrally administered hypertonic NaCl, we examined the effects of a vasopressin antagonist on blood pressure, heart rate, plasma levels of catecholamines, cortisol and renin activity in anesthetized dogs. Intracerebroventricular (ICV) injections of 0.2 ml of 1.5 M NaCl increased mean arterial blood pressure (+29.7 +/- 3.0 mmHg, mean +/- SE), heart rate (+27.9 +/- 7.0 beats/min), plasma concentrations of vasopressin (+48.9 +/- 8.2 pg/ml), norepinephrine (+40.0 +/- 6.2 pg/ml), epinephrine (+231.4 +/- 21.4 pg/ml) and cortisol (+5.3 +/- 1.1 micrograms/dl) and decreased plasma renin activity (-2.0 +/- 0.4 ng/ml/hr). An intravenous vasopressin antagonist, d(CH2)5Tyr(Me)AVP, at a dose of 10 micrograms/kg, attenuated the pressor response and augmented the heart rate response to ICV 1.5 M NaCl. The vasopressin antagonist also augmented the change in plasma norepinephrine and significantly attenuated the responses of cortisol and renin. Baseline levels of these variables were not altered by the vasopressin antagonist except for an increase in renin activity. Two injections of hypertonic NaCl without any pretreatment produced similar cardiovascular and hormonal responses. These results suggest that vasopressin contributes not only to an increase in blood pressure, but also to changes in the sympathetic nervous system, the hypothalamo-adrenocortical axis and the peripheral renin-angiotensin system in response to a central sodium stimulus.

Successful pregnancy and delivery in a patient with neurogenic orthostatic hypotension and achalasia: A case report.

A successful pregnancy and delivery in a patient with neurogenic orthostatic hypotension and a past medical history of achalasia is described. Surprisingly, she was free from orthostatic hypotension during the last trimester, though the evaluation of adrenergic function by measurements of changes in plasma norepinephrine on standing and by the response of blood pressure to infused norepinephrine revealed no difference between function before pregnancy and that during the last trimester. Orthostatic hypotension started again just after delivery.

Preload, adrenergic activity, and aortic compliance in normal and hypertensive patients

Aortic compliance is a major determinant of systolic blood pressure and of impedance to left ventricular ejection. However, little is known about its regulating factors. To assess the effects of preload and adrenergic activity on aortic compliance, we studied 10 normal subjects and nine untreated hypertensive patients at rest and during lower body negative pressure. Aortic compliance was measured invasively from the diastolic decay of the aortic pressure tracing and systemic vascular resistance. Preload was decreased stepwise by lower body negative pressure (−5 to −40 mm Hg) while adrenergic activity was assessed by the change in plasma norepinephrine at a maximum level of negative pressure suction. At rest, aortic compliance was lower in hypertensive subjects compared with its value in normal individuals (0.048 ± 0.012 [SD] versus 0.071 ± 0.009 units, p < 0.001) but correlated inversely with systolic blood pressure in both groups ( r = −0.64 in normotensive individuals, r = −0.83 in hypertensive subjects, r = −0.88 for the whole group, p < 0.001 for all). Whereas resting pulmonary wedge pressure was higher in hypertensive subjects compared with normal individuals (16 ± 4 [SD] versus 11 ± 3 mm Hg, p < 0.05), resting plasma norepinephrine levels were not different between the two groups (261 ± 139 versus 251 ± 103 pg/ml). Neither of these two resting indices correlated with baseline aortic compliance in both normotensive individuals and hypertensive patients. During lower body negative pressure (LBNP), cardiac filling pressure (right atrial pressure and pulmonary wedge pressure) as well as cardiac output decreased in the two groups. Total peripheral resistance and plasma norepinephrine increased in the two groups, indicating normal adrenergic function. The differences in these changes between the two groups were nonsignificant. On the other hand, the increase in heart rate was significant only in the normal group. In both normal individuals and hypertensive subjects, aortic compliance decreased during LBNP, but this decrease did not attain statistical significance in the hypertensive population. Our findings demonstrate that arterial compliance may be modulated in normal subjects more than in hypertensive patients; this difference in behavior may reflect differences in “reactivity” of arterial compliance to hemodynamic and neurohumoral changes and may raise questions relevant to treatment of systolic hypertension.

Relation between plasma norepinephrine and response to medical therapy in men with congestive heart failure secondary to coronary artery disease or idiopathic dilated cardiomyopathy

This study examines the relation between the change in clinical status and the change in plasma norepinephrine concentration in patients with congestive heart failure (CHF) receiving standard medical therapy. Hemodynamic measurements in 11 patients with CHF (ejection fraction 19 ± 4%) were obtained before and immediately after the administration of digoxin and angiotensin-converting enzyme inhibitors. Patients were then followed for 1 year. Clinical status was determined using the Boston Clinical Heart Failure scoring system. Of the 11 patients, 6 demonstrated significant clinical improvement after therapy, based on the Boston score, over a 1-year period. Five patients did not respond to therapy: 4 died and the remaining patient had worsening CHF. There was no difference between responders and nonresponders in either baseline hemodynamics or acute response to the administration of digoxin and an angiotensin-converting enzyme inhibitor. In the patients who improved, plasma norepinephrine decreased from 706 ± 235 to 545 ± 223 pg/ml (p = 0.08) after 1 year of medical therapy. In patients whose CHF worsened or who died, plasma norepinephrine increased from 715 ± 275 at baseline to 1,237 ± 671 pg/ml at their last measurement (p = 0.06). Although at baseline the plasma norepinephrine levels were similar in both groups of patients, a significant difference between responders and nonresponders was observed at final follow-up (p < 0.002). Change in plasma norepinephrine correlated with change in CHF score (r = 0.79, p < 0.004). Thus, in patients with CHF, serial measurements of plasma norepinephrine correlate with changes in cynical status.

A SYMPATHETIC COMPONENT OF BAROREFLEX FUNCTION IN PATIENTS WITH ESSENTIAL HYPERTENSION

1. The baroreflex-mediated changes in plasma norepinephrine (NE) and heart period (RR interval) to phenylephrine (PE)-evoked pressor and nitroprusside (NP)-evoked depressor stimulations were studied in 19 patients with chronic essential hypertension, 12 with borderline hypertension and in 11 age-matched normal controls. 2. Intravenous infusion of PE at a rate of 0.25-1.0 microgram/kg/min induced dose-related increases in mean arterial pressure (MAP) and in RR interval and a decrease in plasma NE. Similarly, NP infusion at a rate of 0.1-0.4 microgram/kg/min evoked the opposite changes in each variable. The reflex sensitivity was defined as the slope of linear regression between the changes in RR interval and MAP (RR/MAP) and between those in plasma NE (% of the baselines) and MAP (%NE/MAP). 3. Both RR/MAP and %NE/MAP for pressor and depressor stimulations were reduced below values found in normal subjects, in both chronic and borderline hypertensives. 4. The values of %NE/MAP was negatively related to the basal plasma NE during falls in blood pressure (r = -0.401, P less than 0.05). 5. The %NE/MAP may be a useful index of the sympathetic component of baroreflex sensitivity. A decrease in %NE/MAP in hypertensive and borderline hypertensive patients suggests a blunted sensitivity of the sympathetic constrictor reflexes.

The influence of rapid potassium administration on hemodynamics and endogenous catecholamine production during extracorporeal circulation

In a prospective randomized double-blind study, the peripheral vascular effects of potassium chloride (KCl) and potassium-magnesium-aspartate (KMA) were compared. Twenty patients undergoing coronary artery bypass graft surgery received either 12 mmol of KCl (n = 10) or 12 mmol of KMA (n = 10) into the oxygenator of the heart-lung machine during extracorporeal circulation (ECC). The most striking difference between these two solutions was vasoconstriction following KCl administration and vasodilation after KMA injection. In the KMA group, decreases of perfusion pressure (MAP) and systemic vascular resistance (SVR), as well as changes in the oxygenator volume (dV), were significant (P less than 0.01) between the first and the fifth minutes. Maximal changes of MAP, from 72 +/- 13 to 59 +/- 12 mmHg (mean +/- SD), and SVR were recorded in the first and second minutes. Oxygenator volume changes reached their maximum (285 +/- 163 mL) in the tenth minute. In the KCl group, maximal increases in MAP, from 70 +/- 16 to 81 +/- 20 mmHg (mean +/- SD), and SVR were found in the fourth minute. Maximal changes in dV (300 +/- 315 mL) were measured in the tenth minute. Plasma epinephrine levels, which were already elevated during ECC, showed further increases in all cases in the KCl group and in most of the cases in the KMA group. The change in plasma epinephrine concentration following KCl injection was significant (P less than 0.01). No characteristic change in plasma norepinephrine was found in either of the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dobutamine on plasma potassium in congestive heart failure secondary to idiopathic or ischemic cardiomyopathy

Dobutamine was administered in a dose of 10 ± 1 μg/kg/mm to 13 patients with severe idiopathic or ischemic dilated cardiomyopathy. Acute hemodynamic improvement was noted in all patients. All patients had a significant decrease in plasma potassium (4.6 ± 0.1 to 4.2 ± 0.2 mEq/liter, p < 0.0001) at peak infusion. The decrease in potassium persisted for at least 45 minutes after discontinuing the infusion. Three patients had exacerba tion of baseline ventricular arrhythmias that resolved with infusion discontinuation. Changes in plasma norepinephrine could not explain the potassium decrease or arrhythmia production, which also significantly decreased in these patients (771 ± 123 to 524 ± 73 pg/ml, p < 0.01). It is concluded that dobutamine causes a significant decrease in plasma potassium and that the decrease persists at least 45 minutes after the infusion is discontinued.

Changes in Serum Concentrations of Taurine and Other Amino Acids in Clinical Antihypertensive Exercise Therapy

Thirty-one Japanese with essential hypertension were divided into training (n = 21) and non-training (n = 10) groups. Physical training of 10 weeks was instituted after 4 or more weeks of observation, and changes in blood pressure and serum concentrations of taurine and other amino acids were investigated. The workload in physical training was predetermined by the submaximal multistage graded exercise test on a bicycle ergometer, and the blood lactate threshold which reflects approximately 40-60% of maximal oxygen uptake was chosen. The hypertensive patients underwent bicycle ergometer training for 60 minutes, three times a week for 10 weeks. Blood pressures were significantly decreased by 14.8/6.6 mmHg in systole/diastole in the training group, but not in the non-training group. Serum concentrations of taurine and cystine were increased significantly by 26% and 287%, in the training group. Increase in serum asparagine (11%), histidine (6%) and lysine (7%) concentrations was also significant, only in the training group. Plasma norepinephrine level and whole blood and plasma volumes were significantly reduced. The change in serum taurine level was significantly negatively correlated with the change in plasma norepinephrine. In addition there was a significant positive correlation between the change in plasma norepinephrine and the change in diastolic blood pressure in the training group. Based on these results, the increase in serum taurine which is known for its antihypertensive activity could contribute, at least in part through the reduction in plasma norepinephrine level, to the antihypertensive effect of exercise.

Functional Relationship Between Platelet α2-Adrenoceptors and Sympathetic Nerve Activity in Man

Functional relationships between platelet alpha 2-adrenoceptors and sympathetic nerve activity were studied in patients with essential hypertension (n = 23), primary aldosteronism (n = 10), and normal subjects (n = 12). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of 3H-yohimbine on platelet membranes and resting plasma norepinephrine (NE) were similar among these groups of subjects. In all subjects combined, Bmax values were correlated positively (r = 0.471, p less than 0.01) to resting plasma NE and negatively (r = -0.531, p less than 0.01) to the changes in plasma NE when subjects were moved from lying to standing. A 2-4 week treatment with guanabenz or bethanidine induced a parallel fall of both Bmax and plasma NE, whereas administration of reserpine caused a similar fall of plasma NE but Bmax remained unchanged. Kd values were not changed after any of these treatments. The results support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than plasma NE per se. This hypothesis seems quite reasonable when it is extended to the presynaptic alpha 2-adrenoceptors; otherwise, the negative feedback function on NE release should be lessened and contradictory to its physiological role.

Effect of reducing atrial pressure on atrial natriuretic factor and vasoactive hormones in congestive heart failure secondary to ischemic and nonischemic dilated cardiomyopathy

The effect of an acute and sustained reduction in atrial pressure on atrial natriuretic factor (ANF) and vasoactive hormone secretion was studied in 9 patients with congestive heart failure (CHF). Intravenous nitroglycerin was titrated to reduce the pulmonary artery wedge pressure by 30 to 50% and maintain this reduction for 4 hours. After 60 minutes of nitroglycerin administration, the mean decrement in wedge pressure was 10.0 ± 1.7 (standard error) mm Hg (35%) and plasma ANF was 65.3 ± 13.9 pmol/liter (35%). The initial decrease, sustained reduction and later increase in plasma ANF levels closely paralleled the changes in pulmonary arterial wedge (r = 0.94, p < 0.0001) and right atrial pressures (r = 0.91, p < 0.0001) during and immediately after the nitroglycerin infusion. Plasma aldosterone and cortisol levels increased during the first 2 hours of the nitroglycerin infusion, but there was little change in plasma norepinephrine or plasma renin activity. Although levels were elevated in CHF, plasma ANF still responded rapidly to changes in atrial pressure. A sustained reduction in pressure produced a sustained reduction in ANF levels. These findings provide further support for a regulatory role of ANF, even in chronic CHF.

Reproducibility of haemodynamic and plasma catecholamine responses to isometric exercise and mental arithmetic in normo- and hyper-tensive subjects.

1. To determine the reproducibility of a mental arithmetic stress test and a handgrip exercise test, we studied the responses of blood pressure, heart rate, forearm blood flow and plasma catecholamines on two occasions, with an interval of at least 1 week, in 24 normotensive and 22 hypertensive subjects. 2. The SE of a single observation of the percentage changes of blood pressure ranged from 3.9 to 9.3% in normotensive subjects and from 3.9 to 7.4% in hypertensive subjects in both tests. For heart rate, these values were 4.9-12.3% in the normotensive subjects and 4.8-5.7% in the hypertensive subjects. However, there was a wide individual scatter of these haemodynamic responses during both tests. The forearm blood flow, only measured during mental arithmetic, had an SE of a single observation of 33.7%. 3. In 10 normotensive subjects the SE of a single observation of the change in plasma noradrenaline was 0.16 nmol/l during handgrip exercise and 0.09 nmol/l during mental arithmetic. The corresponding values for plasma adrenaline were 0.04 and 0.05 nmol/l. 4. In conclusion, although both tests showed a rather low SE of a single observation for the blood pressure and heart rate responses in normo- and hyper-tensive subjects, there was a considerable individual variability. If related to the mean forearm blood flow responses, the SE of a single observation of the forearm blood flow response was of similar magnitude. The limited intra-individual reproducibility of both tests should be borne in mind when interpreting pharmacological intervention studies or studies evaluating sympathoadrenal reactivity in cardiovascular disorders.

Effects of Infused Norepinephrine and Angiotensin-II on Vasopressin Levels in Humans

Angiotensin II (A-II) has been shown to stimulate plasma arginine vasopressin (AVP) secretion in experimental animals, although offsetting effects from a rise in arterial pressure may obscure the effect. A rise in plasma norepinephrine (NE) may have several effects on plasma AVP because of changes in arterial pressure and central adrenergic stimulation. As little data exist concerning these neurohumoral interrelationships in humans, the current investigation was performed to examine the role of acute changes in plasma NE and A-II in the control of arginine vasopressin (AVP). The question is of potential importance because of diffuse disturbances in neurohumoral control in diseases such as hypertension and congestive heart failure. We measured heart rate, arterial pressure, and plasma AVP during 2.5 and 5.0 micrograms/min infusions of NE, and during .05 and .10 micrograms/kg/min infusions of A-II. NE increased mean blood pressure from 81 +/- 11 mm Hg to 87 +/- 16 mm Hg at 2.5 micrograms/min and to 93 +/- 16 mm Hg at 5.0 micrograms/min (p less than .001). Heart rate was unchanged during the 2.5 micrograms/min infusion but declined from 58 +/- 9 beats/min to 54 +/- 9 beats/min during the 5.0 micrograms/min infusion (p = NS). Plasma AVP, 3.0 +/- 0.9 pg/mL, did not change. During A-II infusions, mean arterial pressure increased from 81 +/- 13 mm Hg to 92 +/- 17 mm Hg and 112 +/- 21 mm Hg at the two rates (p less than .001); heart rate declined from 61 +/- 6.8 beats/min to 59 +/- 9.1 beats/min and 56 +/- 11.3 beats/min (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Reflex control of coronary vascular tone by cardiopulmonary receptors in humans

To examine whether cardiopulmonary receptors participate in the reflex control of coronary vascular resistance, systemic and coronary hemodynamics were assessed before and during -10 mm Hg lower body negative pressure in eight normal subjects and eight hypertensive patients with left ventricular hypertrophy. In both study groups, lower body negative pressure induced a significant decrease in right atrial pressure, left ventricular filling pressure and cardiac output, an increase in systemic vascular resistance and no change in mean arterial pressure and heart rate. In normal subjects, there was also a significant increase in plasma norepinephrine concentration (from 294 ± 39 to 421 ± 47 pg/ml, p < 0.01). This increase was accompanied by a reduction in coronary blood flow, assessed by the continuous thermodilution method (from 101 ± 5 to 79 ± 4 ml/min, p < 0.05). An increase in coronary vascular resistance (from 0.865 ± 0.1 to 1.107 ± 0.1 mm Hg/ml per min, p < 0.05) and in myocardial oxygen consumption was detected in normal subjects during cardiopulmonary baroreceptor unloading. In contrast, in hypertensive patients, −10 mm Hg lower body negative pressure failed to induce any change in plasma norepinephrine, coronary blood flow or vascular resistance.Intravenous propranolol administration caused no significant change in the systemic hemodynamic response to −10 mm Hg lower body negative pressure in either study group, but it did abolish the decrease in coronary flow and the increase in plasma norepinephrine, coronary vascular resistance and myocardial oxygen consumption observed in normal subjects in control conditions. Finally, propranolol did not modify the systemic and coronary hemodynamic responses either to lower body negative pressure in hypertensive patients or to a 60 mm Hg increase in neck tissue pressure in both groups of subjects.These results suggest that cardiopulmonary baroreceptors participate in the reflex control of coronary vascular tone in normal subjects and that this response is abolished in hypertensive patients with left ventricular hypertrophy as a result of an altered cardiopulmonary receptor function.

Plasma and urinary catecholamines in salt-sensitive idiopathic hypertension.

Nineteen patients with normal renin idiopathic hypertension were arbitrarily classified as salt-sensitive or salt-resistant depending on whether their mean arterial pressure did or did not increase by 8% or more when sodium intake was increased. The responses of the two subsets and of five normal subjects to sodium intakes of 9, 109, and 249 mEq/day given for 7 days were as follows: The salt-sensitive subjects retained more sodium than normal and plasma or urinary norepinephrine did not decrease when they were given a high sodium intake; urinary dopamine was normal but did not increase normally when sodium intake was increased. The salt-resistant subjects excreted sodium normally and plasma and urinary norepinephrine was decreased by 30 and 37%, respectively, when they were given a high sodium intake; urinary dopamine was supernormal and did not increase further when sodium intake was increased. Cumulative sodium retention during the high sodium intake was directly related to the percentage of change in plasma norepinephrine in the hypertensive subjects, suggesting that renal adrenergic activity was a factor in the impaired sodium excretion in the salt-sensitive patients. Cumulative sodium retention and the percentage of change in plasma norepinephrine were inversely related to urinary dopamine in the hypertensive subjects, suggesting that increased formation of dopamine in renal and neural tissue in the salt-resistant subjects may have been responsible for the differences between the subsets in renal and adrenergic responses to a high sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and renal hemodynamic effects of celiprolol in essential hypertensives

To evaluate the humoral and hemodynamic (both systemic and renal) effects of celiprolol and to assess whether these effects are at least partially due to the activation of dopamine (DA) receptors, 9 outpatients with mild to moderate uncomplicated essential hypertension, without any therapy for at least 3 weeks, received celiprolol (400 mg once daily) and placebo, each for 1 month, according to a double-blind randomized trial pattern. At the end of each treatment period, blood pressure, heart rate, renal plasma flow, glomerular filtration rate, plasma renin activity, plasma aldosterone and plasma norepinephrine were measured after administration of saline solution and intravenous metoclopramide. Compared with placebo, celiprolol significantly reduced mean blood pressure, heart rate and plasma norepinephrine. Plasma renin activity showed a tendency toward a reduction during celiprolol treatment, which was not associated with changes in plasma aldosterone. Despite the decrease in mean blood pressure, renal plasma flow did not change, so that renpoascular resistances were significantly reduced. Glomerular filtration rate was unchanged and the filtration fraction showed a trend toward a reduction during celiprolol treatment. Percent decrements of renovascular resistances and of mean blood pressure induced by celiprolol tended to correlate with changes in plasma norepinephrine. Metoclopramide did not influence the hemodynamic (systemic and renal) effects of celiprolol nor plasma renin activity and plasma norepinephrine, and it increased aldosterone levels to a similar extent before and after administration of celiprolol. However, during celiprolol treatment, metoclopramide tended to increase renal plasma flow, whereas during placebo treatment renal plasma flow tended to be decreased by metoclopramide. Our data show that the antihypertensive effect of celiprolol is not accompanied by a reduction in renal plasma flow because the drug induces a renal vasodilation proportional to the decrease in blood pressure. The effects of celiprolol on systemic and renal circulation are not mediated by DA receptors, but appear to be related to a reduced sympathetic nervous system activity. However, the observation that DA 2-receptor blockade tends to reduce renal plasma flow during placebo and to increase it after celiprolol suggests an interaction of celiprolol with the regulatory function of presynaptic DA 2 receptors at a renal level. It is speculated that an inhibition of norepinephrine release induced by celiprolol unmasks the autoregulatory role of DA 2 receptors on DA release, and that the resulting increase in DA release may cause renal vasodilation.

Long-term Effects of Parathyroidectomy on Cardiac and Autonomic Nervous System Functions in Haemodialysis Patients

Ten patients receiving regular haemodialysis therapy who underwent parathyroidectomy for secondary hyperparathyroidism were investigated to evaluate the effects of parathyroid hormone on left ventricular and autonomic nervous system functions. The study which included M-mode echocardiography and autonomic nervous system tests (hormonal and cardiovascular response to the postural test, cold pressor test, handgrip test, diving reflex test and Valsalva manoeuvre) were performed prior to parathyroidectomy, and 5-8 months after, on a nondialysis day. The cardiovascular response and plasma noradrenaline changes to postural test remained unchanged following parathyroidectomy. The resting heart rate decreased from 73.1 +/- 2.4 to 66.4 +/- 2.3 beats/min (P less than 0.05) but mean blood pressure did not change post-parathyroidectomy. Mean blood pressure and heart rate changes during the cold pressor test, handgrip test, diving test and Valsalva manoeuvre were unaffected by parathyroidectomy. End-diastolic and end-systolic dimensions, fractional fibre shortening, mean velocity of fibre shortening and the ratio of the pre-ejection period to the left ventricular ejection time were normal prior to parathyroidectomy and remained unchanged following it. This study suggests that the reduction in parathyroid hormone concentrations obtained by parathyroidectomy does not significantly modify heart function and autonomic nervous system activity in the long term.

Enhanced blood pressure response to isometric handgrip exercise in patients with essential hypertension: effects of propranolol and prazosin.

To elucidate whether a difference exists in blood pressure (BP) elevation during isometric handgrip exercise (IHG) between essential hypertensives (EHT) and normotensives (NT), IHG was carried out in 12 NT and 46 EHT under constant sodium intake using a new instrument. The acute effects of propranolol and prazosin on IHG were also examined in EHT. The change in systolic BP (delta SBP) during IHG in EHT, delta SBP = 61 +/- 21 mmHg, was markedly greater than that in NT, delta SBP = 28 +/- 4 mmHg. Among EHT, delta BP increased with increasing severity of hypertension. Neither the changes in plasma norepinephrine nor in epinephrine during IHG showed significant differences between EHT and NT. The pressor response during IHG could not be suppressed by propranolol, but about 30% suppression of BP was observed during IHG with prazosin. It is concluded from these findings that EHT have an exaggerated BP response to IHG that is due to increased post-junctional alpha 1-adrenoceptors.

Effects of the cold pressor test on muscle sympathetic nerve activity in humans.

The purpose of this study was to determine the effects of the cold pressor test on sympathetic outflow with direct measurements of nerve traffic in conscious humans and to test the strength of correlation between sympathetic nerve discharge and the changes in arterial pressure, heart rate, and plasma norepinephrine. In 25 healthy subjects, arterial pressure, heart rate, and muscle sympathetic nerve activity were measured with microelectrodes inserted percutaneously into a peroneal muscle nerve fascicle in the leg during immersion of the hand in ice water for 2 minutes. Arterial pressure rose steadily during the first and second minutes of the cold pressor test. Muscle sympathetic activity (burst frequency X amplitude) did not increase in the first 30 seconds of the test but increased from 230 +/- 27 to 386 +/- 52 units (mean +/- SE, p less than 0.05) by the end of the first minute of the test and to 574 +/- 73 (p less than 0.01) during the second minute. In contrast, heart rate increased maximally during the first 30 seconds of the cold pressor test and returned to control during the second minute. The increases in heart rate were abolished by beta-adrenergic blockade. The increases in muscle sympathetic activity during the cold pressor test were correlated with the increases in both mean arterial pressure (r = 0.86, p less than 0.01) and peripheral venous norepinephrine (r = 0.72, p less than 0.05); however, large changes in nerve traffic were associated with small changes in plasma norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

A Clinical Study of Sensitivity to Sodium Nitroprusside during Controlled Hypotensive Anesthesia in Young and Elderly Patients

Aging has important effects on the cardiovascular system; baroreceptor reflex function decreases and the elderly are more resistant to both β-receptor agonists and antagonists. The purpose of the present clinical study was to determine the relationship between age and sensitivity to sodium nitroprusside in 16 patients during deliberate hypotensive anesthesia by determining the blood pressure changes in young and elderly patients to incremental increases in dose of sodium nitroprusside. A dose-response curve relating change in mean blood pressure to dose of sodium nitroprusside (μg·kg−1·min−1) was constructed for each patient; the slope of this line is a measure of “sensitivity.” The change in mean arterial blood pressure per μg·kg−1·min−1 nitroprusside dose (i.e., slope), showed a significant correlation with age (r = 0.766, P < 0.001), demonstrating that sensitivity to sodium nitroprusside increases with advancing years. The maximum change in heart rate produced by nitroprusside showed a reciprocal correlation with age (r = −0.791, P < 0.001). There was no significant correlation between age and maximum change in plasma norepinephrine or epinephrine concentrations during nitroprusside infusion. The increased sensitivity to nitroprusside might have been due to 1) diminished baroreflex activity, 2) resistance of cardiac adrenergic receptors to catecholamine stimulation, or 3) alteration in sensitivity to the direct vasodilating effects of sodium nitroprusside. Whatever the mechanism, however, this clinical study has shown that lower doses of nitroprusside should be used in elderly patients to achieve the same degree of hypotension achieved in younger patients.

The baroreflex-mediated changes in plasma norepinephrine and heart rate in patients with essential hypertension.

Baroreflex sensitivity was evaluated in 19 patients with essential hypertension (EH), 8 patients with borderline hypertension (BH) and 12 age-matched normal controls (N), by measuring the reflex-mediated changes in plasma norepinephrine (NE) and heart rate (RR interval) while a phenylephrine hydrochloride or a sodium nitroprusside solution was infused in graded doses for a total of 24 minutes. Changes in RR interval and plasma NE showed a significant linear correlation to those in mean arterial pressure (MAP) in every subject studied. The slopes of RR/MAP and %NE/MAP tended to be reduced in EH and BH patients during both pressor and depressor stimulations. There was a significant (p less than 0.01) inverse correlation between the basal MAP levels and RR/MAP or %NE/MAP except for %NE/MAP during pressor stimulation. Fifteen minutes after the pressor stimulation was stopped, MAP and RR interval in each group tended to be greater than their baselines. Plasma NE remained significantly (p less than 0.01) depressed in N and BH subjects while those in EH returned to their baselines. When pressor stimulations were repeated twice at intervals of 15 minutes in hypertensive subjects, the second response curves of MAP-RR interval tended to shift slightly to the right while the slopes of the second response curves of plasma NE were significantly (p less than 0.05) reduced compared with the first ones. These findings indicate that an inability of the baroreflex to produce a sustained suppression of sympathetic nerve activity associated with an efficient ability to reset at the higher pressure levels in EH patients results in a continued tendency for blood pressure to rise and contributes to the development of hypertension.