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Biomedical subjects

S Julius

Publications and source records attributed to S Julius.

At least 145 records · Page 8Linked to original sources
PubMed1987

Role of the sympathetic nervous system in the pathophysiology of cardiovascular disease.

Psychosomatic elements, behavior, and sympathetic overactivity are presumed to underlie many cardiovascular diseases; the most investigated conditions are borderline hypertension and type A/B behavior. Many patients with borderline hypertension show signs of hyperkinetic circulation, that is, elevated heart rate and cardiac index. This elevation is neurogenic, since it can be abolished with a combination of beta-adrenergic and parasympathetic blockade. Response to such stepwise blockade shows a larger beta-adrenergic and a lower parasympathetic change in cardiac tone, characteristic of the functional organization of the medullary integrative centers of cardiovascular control. The most likely cause for this abnormal integration is psychosomatic. These patients may be expected to respond to treatment with behavioral and/or cardioselective beta-adrenergic blocking agents. There is little doubt that type A behavior is a predictor of coronary heart disease. The description of the pathophysiology of these transient but characteristically excessive cardiovascular episodes is difficult, however. Type A individuals do not always hyperreact in the same way; the response can be limited to heart rate, blood pressure, or occasionally exaggerated urinary or plasma catecholamine responses. In our laboratory we concentrated on steady markers of type A behavior. Type A subjects had reproducibly larger pupil size--indicative of increased sympathetic arousal--higher heart rate and diastolic blood pressure, and significantly elevated platelet epinephrine values when challenged by a mental task. Treatment with behavioral methods, beta-blocking agents, or both might be useful for prevention of coronary heart disease in type A individuals.

Drug Evaluation↗
PubMed1987

Research utility of noninvasive methods for measurement of cardiac output.

Two noninvasive methods of cardiac index (Q) determination, pulsed Doppler echocardiography (QDop), and CO2 rebreathing (QCO2) were compared to dye dilution in eight normal volunteers. Measurements of Q were made by dye dilution (QDD) and the two noninvasive techniques under the following conditions: supine rest, after inflation of cuffs around the thighs, 35-degree head-up tilt, supine rest repeated, during constant isoproterenol infusion, and after an intravenous bolus of propranolol. When mean Q values of the group for each intervention were compared, close agreement was observed between dye dilution and each noninvasive method (QDOP = 1.08 QDD - 0.07 L/min X m2, r = 0.99, SEE = 0.02; QCO2 = 0.68 QDD + 0.84 L/min X m2, r = 0.97, SEE = 0.02). Fair correlations were achieved when all 48 paired observations were analyzed (QDop = 1.00 QDD + 0.17 L/min X m2, r = 0.89, SEE = 0.17; QCO2 = 0.71 QDD + 0.77 L/min X m2, r = 0.79, SEE = 0.20). However, the Doppler ultrasound technique was significantly more precise in quantitating changes in Q in individual patients. These results demonstrate that estimates of Q can be made with reasonable accuracy by either CO2 rebreathing or Doppler echocardiography. However, the Doppler technique is a much more accurate means of quantitating acute changes in Q.

Adult↗
PubMed1987

Antihypertensive and hypotensive effects of atrial natriuretic factor in men.

Synthetic atrial natriuretic factor (ANF) was administered in ascending doses (0.03, 0.20, 0.45 microgram/kg/min) to eight mildly essential hypertensive men on high (200 mEq/day) or low (10 mEq/day) sodium diets. Responses of blood pressure, heart rate, urinary volume and electrolyte excretion, renin, and aldosterone were measured. For the entire group, ANF lowered blood pressure and increased heart rate during the 0.20 and 0.45 microgram/kg/min infusions, and the antihypertensive effect of the peptide persisted for at least 2 hours after the infusions ended. Four patients (2 at 0.20 microgram/kg/min and 2 at 0.45 microgram/kg/min) experienced sudden bradycardia and hypotension at the end of or shortly after completion of ANF infusion. Renal excretion of water, sodium, chloride, calcium, and phosphorus increased in a dose-dependent fashion in response to infused ANF. Patients on the 200 mEq/day sodium diet had greater increases in urinary volume (11.1 +/- 2.8 vs 3.0 +/- 2.0 ml/min; p less than 0.05), sodium (870 +/- 134 vs 303 +/- 27 microEq/min; p less than 0.05), and chloride (801 +/- 135 vs 176 +/- 75 microEq/min; p less than 0.02) compared with patients on the low sodium diet. The apparent direct suppressive effect of a 0.03 microgram/kg/min infusion of ANF on renin and aldosterone levels was overcome at higher doses by counterregulation provoked by the depressor action. Renin was slightly (-12%) suppressed during the 0.03 microgram/kg/min infusion of ANF but increased at the 0.20 (+50%) and 0.45 microgram/kg/min (+90%; p less than 0.03) rates. Aldosterone declined significantly during the 0.03 microgram/kg/min infusion (-45%; p less than 0.01) of ANF but not during the two higher dose infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Red blood cell Li+-Na+ countertransport, Na+-K+ cotransport, and the hemodynamics of hypertension.

Red blood cell Li+-Na+ countertransport and Na+-K+ cotransport activities, home blood pressure, invasive systemic hemodynamics, and limb venous compliance were measured in 65 white men (23 normotensive, 22 borderline hypertensive, and 20 mild essential hypertensive subjects). Li+-Na+ countertransport activity was positively and significantly correlated with subject-determined home systolic blood pressure (r = 0.31, p less than 0.02) and with directly measured systolic (r = 0.29, p less than 0.02) and diastolic (r = 0.27, p less than 0.03) blood pressures in the hemodynamic laboratory, independent of potential confounding variables. Analysis of the hemodynamic determinants of blood pressure revealed a significant positive correlation of countertransport with vascular resistance (r = 0.30, p less than 0.02) but not with cardiac output or cardiac index. High red blood cell Na+-K+ cotransport activity was not independently associated with hypertension or with a characteristic hemodynamic pattern but was related to decreased venous compliance. Red blood cell Li+-Na+ countertransport deserves further study as a marker for the genetic substrate of human essential hypertension. Red cell Na+-K+ cotransport may be altered secondarily by factors related to high blood pressure and seems to be a valid marker for abnormalities of the venous system in hypertension.

Adult↗
PubMed1987

Mechanism of increased alpha adrenergic vasoconstriction in human essential hypertension.

Multiple components of vascular alpha adrenergic responsiveness were investigated in twenty-four men with mild hypertension and eighteen age- and weight-matched normotensive controls. Arterial plasma norepinephrine (paNE), an index of sympathetic drive, was increased in hypertensives compared to normotensives (mean +/- SE), 199 +/- 24 vs. 134 +/- 11 pg/ml, P less than 0.02. The effective concentration of intra-arterial (iaNE) increasing forearm vascular resistance (FAVR) 30% (NE-EC30, an index of vascular alpha-receptor sensitivity) was similar in normotensives and hypertensives, 9 +/- 1 vs. 13 +/- 3 ng/100 ml per min, respectively, P greater than 0.3. The phentolamine induced reduction in FAVR, an index of vascular alpha-tone, was greater in hypertensives, -21.3 +/- 1.8 vs. normotensives, -14.9 +/- 1.2 U, P less than 0.02. We interpret these data as evidence for normal vascular alpha-receptor sensitivity to norepinephrine in mild hypertensives. Consequently, the increased sympathetic drive in mild hypertensives explains the elevated vascular alpha-tone. Although vascular alpha-receptor sensitivity to iaNE was normal, the FAVR responses at high doses (reactivity) were greater in hypertensives to regional infusion of both NE and angiotensin II. This "nonspecific" enhancement of vascular reactivity is probably explained by structural vascular changes in hypertensives.

Adult↗
PubMed1987

The heart and the regulation of renin.

The cause of the low-renin state in hypertension is unknown. To consider our hypothesis that cardiopulmonary mechanoreceptors suppress renin release in these patients, it was necessary to prove that "low pressure" receptors affected renin levels in man. A series of experiments was performed to selectively alter the stretch (load) on carotid and cardiopulmonary baroreceptors in healthy human volunteers. These studies showed that selectively altering high-pressure baroreceptor load did not affect plasma renin activity. Selectively unloading the low-pressure receptors increased plasma renin activity. Simultaneous unloading of both baroreceptors caused the largest increases in renin activity. While the data indicated an interaction of high- and low-pressure receptors on the neural regulation of renin release, we interpreted these results as evidence for a predominant influence of cardiopulmonary mechanoreceptors on the neurogenic regulation of renin secretion in man.

Arteries↗
PubMed1986

Decreased venous distensibility and reduced renin responsiveness in hypertension.

Abnormalities of renin release and of venous distensibility have been described in essential hypertension. We have postulated that decreased venous distensibility could contribute to the blunted renin response to upright posture in hypertension. Stiffer veins might prevent venous pooling in the lower extremities, which in turn might affect the stretch on cardiopulmonary mechanoreceptors, thereby influencing the reflex release of renin. We investigated this hypothesis in the present study of 47 patients with mild hypertension and 26 (male) healthy volunteers of similar age and race. To induce isolated changes in the stretch of cardiopulmonary mechanoreceptors, systemic hemodynamics were measured before and after thigh cuff inflation at 60 mm Hg for 30 minutes. Cardiac output was determined by dye dilution. Before the intervention, variable thigh cuff pressures were used to measure venous pressure volume with mercury-in-Silastic strain gauge plethysmography. Venous distensibility was diminished in hypertension, as evidenced by a shift in the calf venous volume/pressure curve toward the pressure axis. During the 30-minute experiment, the hypertensive subjects had less blood pooling in their legs in response to thigh cuff inflation, as compared with the control subjects. The hemodynamic and renin responses reflected this diminished effect of thigh cuff inflation on venous return. The smaller increase of renin in the hypertensive group was associated with a smaller fall in the stroke index and right atrial pressure; the reflex rise in the heart rate was also decreased. By pooling blood in the lower extremities, thigh cuff inflation simulates upright posture. It is customary to classify the renin status of hypertensive patients according to the renin response to upright posture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Pharmacologic reduction of sympathetic drive increases platelet alpha-2-receptor number.

Several lines of evidence implicate sympathetic nervous system involvement in the pathophysiology of essential hypertension in man. Extrapolations are frequently made from in vitro measurements of plasma catecholamine levels to the physiologic role of the sympathetic system in hypertension. We assessed the utility and validity of such extrapolation from in vitro to in vivo measures of adrenergic function. Addition of guanadrel to diuretic therapy in 11 patients with essential hypertension reduced supine intra-arterial blood pressure from 135 +/- 14/76 +/- 9 to 127 +/- 13/67 +/- 5 mm Hg (P less than 0.02). Supine heart rate was also reduced, from 77 +/- 14 to 63 +/- 13 bpm (P less than 0.001). Plasma norepinephrine levels fell from 303 +/- 107 to 170 +/- 46 pg/ml (P less than 0.01). Platelet alpha 2-receptor number ([3H]yohimbine maximal binding) increased from 204 +/- 77 to 301 +/- 150 fmol/mg (P less than 0.02). The pupillary mydriatic response to phenylephrine and the forearm arterial vasoconstrictor response to intra-arterial norepinephrine did not change. Thus guanadrel reduced blood pressure by decreasing sympathetic tone. In this milieu of low sympathetic activity the platelet alpha 2-receptor number increased, but physiologic responses to exogenous alpha-agonists did not change. Caution is therefore advised when extrapolating from in vitro measurement of plasma catecholamine levels and platelet alpha 2-receptor number to the in vivo physiologic significance.

Adult↗
PubMed1985

Methods for measuring vascular and nonvascular alpha-receptor sensitivity in humans.

Since increased alpha-adrenergic reactivity may participate in the pathophysiology of essential hypertension, methods for accurately assessing in vivo alpha-receptor sensitivity in humans might be useful. The goals of this study were to employ previously used methods, namely pupillometry and local forearm intraarterial infusions, to assess alpha-receptor sensitivity, create an in vivo environment of decreased sympathetic drive (plasma norepinephrine) and increased alpha-receptor number (platelet alpha 2), in which increased alpha-receptor sensitivity to exogenous agonists might occur. Five patients with minimally elevated blood pressure (139 +/- 5/90 +/- 4 mm Hg) while on diuretic monotherapy completed assessment of biochemical and physiologic variables on diuretic alone and again on diuretic and guanadrel. Guanadrel plus diuretic compared with diuretic alone lowered the seated diastolic and standing systolic and diastolic blood pressure. Heart rate was decreased about 10 beats/min. Baseline supine norepinephrine was reduced an average of 40% (from 281 +/- 23 to 168 +/- 16 pg/ml, p = 0.03), and platelet alpha 2-receptors were increased roughly 40% (from 178 +/- 34 to 250 +/- 54 fmol/micrograms, p = 0.07). Despite the expected decrease in sympathetic drive and increase in alpha-receptors (platelet alpha 2), the pupillary mydriatic response to phenylephrine and the forearm vasoconstrictor response to intraarterial norepinephrine were not augmented. The failure to detect increased physiologic responsiveness in the presence of decreased norepinephrine and increased alpha 2-receptor number lends itself to multiple explanations which need to be tested in future research.(ABSTRACT TRUNCATED AT 250 WORDS)

Arm↗
PubMed1985

Hemodynamic effects of angiotensin-converting enzyme inhibitors in essential hypertension: a review.

Angiotensin-converting enzyme inhibitors are vasodilators that exert their beneficial hemodynamic effects in hypertension primarily by withdrawal of the vasoconstricting action of endogenous angiotension II. Although the magnitude of the initial decrease in vascular resistance depends on renin activity, the long-term arterial blood pressure response does not appear to be influenced by initial renin levels. Cardiac output is not significantly altered by angiotensin-converting enzyme inhibition in patients with mild-to-moderate hypertension, but a rise toward normal levels often occurs in patients with severe hypertension or heart failure. Although right and left heart filling pressures are not significantly altered, other evidence suggests that these agents increase venous capacitance. Patients with severe hypertension, for example, have shown increased forearm venous distensibility in response to angiotensin-converting enzyme inhibitors, and a decrease in the ratio of cardiopulmonary blood volume to total blood volume has been demonstrated in normotensive patients with heart failure. Several studies have shown improved renal blood flow after angiotensin-converting enzyme inhibition, suggesting that renal vascular resistance is reduced more than systemic resistance. Reflex tachycardia and other neurohumoral counterregulatory responses occur less frequently than with other vasodilators, because neither the renin-angiotensin-aldosterone nor the autonomic nervous system is activated by angiotensin-converting enzyme inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Vascular hypertrophy in borderline hypertension: relationship to blood pressure and sympathetic drive.

While borderline hypertension increases the chance for cardiovascular disease, most with borderline hypertension will not experience problems. Thus, the risk of intervening probably outweighs benefit for the majority. However, those with target organ damage are probably at higher risk and might benefit from more aggressive management. Therefore, we assessed vascular hypertrophy and average home blood pressures in patients with borderline hypertension which might be of value in therapeutic planning. Minimum forearm vascular resistance (mFAVR) was used as an index of vascular hypertrophy. Comparing ten normotensive controls to twenty individuals with borderline hypertension revealed a significant difference in mFAVR (1.7 +/- 0.06 vs 2.1 +/- 0.1, p less than .05). There were obvious differences in blood pressure between normotensives and borderlines which contributed to differences in mFAVR. However, within the group with borderline hypertension, no relationship was apparent between mean blood pressure and mFAVR, r = 0.13, NS. Among the borderline hypertensives, baseline plasma norepinephrine correlated with mFAVR, r = 0.48, p less than .05, suggesting that the sympathetic nervous system contributes to vascular hypertrophy in this group. In a separate group of individuals with nine normotensives and nine borderline hypertensives we wished to find if average home blood pressure would correlate better with mFAVR than a single laboratory measurement. While both the home (r = 0.56, p less than .05) and laboratory (r = 0.66, p less than .01) MBP correlated significantly with mFAVR, the data did not confirm the hypothesis that the average home blood pressures would better predict the degree of vascular hypertrophy. These data show that a substantial proportion of patients with borderline hypertension have evidence for vascular hypertrophy, sympathetic drive might contribute to vascular hypertrophy in borderline hypertension, average home blood pressures did not aid in separating those with and without evidence for vascular hypertrophy.

Adult↗
PubMed1985

Stress, autonomic hyperactivity and essential hypertension: an enigma.

This review shows that there is ample evidence of a stress-related hypersympathetic state in the early phase (borderline, hyperkinetic) of essential hypertension. These patients have signs of excessive autonomic cardiovascular drive (e.g. large changes in cardiac output, heart rate and pre-ejection period). After autonomic blockade these patients were also prone to suppressing anger and tended to be submissive towards other people. Research to determine whether personality traits are related to hypertension has shown that suppressed anger and submissiveness appear to be more related to sustained blood pressure elevation than to blood pressure variability. Although there is adequate evidence for a relationship between stress, personality and hypertension in borderline hypertension, it is difficult to demonstrate an autonomic nervous system component in established hypertension. Apparently mechanisms of blood pressure elevation change during the natural history of hypertension, and more research to understand the character of these changes is needed.

Blood Pressure↗
PubMed1984

Pharmacologic tools for assessment of adrenergic nerve activity in human hypertension.

Measurement of plasma norepinephrine concentration (plasma NE) has not resolved the role of the adrenergic system in the pathogenesis or maintenance of hypertension. A better picture is gained if plasma NE measurement is combined with the assessment of sympathetic drive and reactivity by the use of specific sympathetic antagonists and agonists. In mild hypertension, the decrease in heart rate and cardiac output after beta-adrenoceptor blockade correlates with the level of plasma NE. In established hypertension, the fall in blood pressure or peripheral vascular resistance after alpha-adrenoceptor blockade is related to plasma NE levels. Similarly, changes in forearm vascular resistance induced by local alpha-adrenoceptor blockage correlates with plasma NE in hypertension. Cardiovascular responsiveness to adrenergic agonists is altered in hypertension. The response to cardiac beta-receptor stimulation decreases during the course of the disease. To the contrary, vascular responses to exogenous NE increase with the progression of the hypertensive disease. Results with total autonomic blockade indicate that in some patients with early or borderline hypertension, increased sympathetic tone is involved in the maintenance of blood pressure. In established hypertension, there is no definite indication of increased sympathetic tone, but the sympathetic nervous system may nevertheless play a prominent role in the maintenance of the blood pressure. A vascular hyperreactivity to adrenergic stimulation is characteristically associated with established hypertension. The nature of this hyperreactivity has not been fully elucidated, but it is very likely that it reflects structural vascular changes in hypertension.

Autonomic Nervous System↗
PubMed1984

Treatment of mild hypertension with progressive muscle relaxation. Predictive value of indexes of sympathetic tone.

Effects of progressive muscle relaxation (PMR) and of attention control were investigated in a prospective randomized trial of borderline or mild hypertensive patients. Both groups received placebo and had the same number of clinic return visits. After 22 weeks the average mean home BP in PMR decreased 3 mm Hg, whereas in controls BP increased 2 mm Hg. Progressive muscle relaxation had no significant effect on the clinic BP. The response to PMR was not uniform. Responders were characterized by faster heart rates and higher plasma norepinephrine levels. The responders also showed a decrease of anxiety scores during the trial. Progressive muscle relaxation is a time-consuming procedure. Blood pressure responses do not substantially exceed the placebo effects in unselected patients. However, relaxation may be suitable for young, anxious patients with mild hypertension who have a high resting sympathetic tone.

Adolescent↗