Biomedical subjects
S Julius
Publications and source records attributed to S Julius.
Antihypertensive and beta-adrenoceptor antagonist action of timolol.
Explore the source record for details and available documents.
Borderline hypertension: clinical and pathophysiologic significance.
Explore the source record for details and available documents.
Clinical and physiological significance of borderline hypertension at youth.
Marginal blood pressure elevation at youth is widely prevalent. Clinically such patients represent a dilemma, since they are at highest risk to develop hypertension and its sequelae, but the risk is not sufficiently strong to mandate antihypertensive medication. The decision as to whether to treat will depend on the presence of other risk factors for hypertension. Multiple and complex pathophysiologic abnormalities have been described in borderline hypertension. A better understanding of the relationship of some of these abnormalities to the development of hypertension is needed.
Renin response to stimulation of cardiopulmonary mechanoreceptors in man.
Plasma renin activity (renin) and hemodynamic response to venous pooling of blood in legs were studied in 24 healthy volunteers and four patients who after bilateral nephrectomy received a functioning renal transplant. Blood pressure cuffs were placed around subjects' thighs and inflated at a pressure 5 mm Hg below the individuals' diastolic pressures. 30 min after thigh cuff inflation, renin significantly increased in all volunteers (mean = 125%). Inflation of cuffs induced a decrease of right atrial pressure, cardiopulmonary blood volume, and cardiac output, but there were no changes in the extra-arterial systolic and diatoloic pressure or in the pressure amplitude. After cuffs were deflated, renin and hemodynamic parameters returned toward normal. In nine volunteers in whom thigh cuff inflation initially elicited renin increases, subsequent intravenous propranolol (0.25 mg/kg) abolished the response to repeated cuff inflation. The renin increase to thigh cuff inflation was absent or suppressed in four patients with a recently transplanted denervated kidney. It is concluded that thigh cuff inflation elicited a reflex-mediated renin increase, and that the reflex stemmed from stimulation of cardiopulmonary mechanoreceptors.
The determinants of plasma-renin activity in essential hypertension.
Plasma-renin activity was studied, under different conditions of sitmulation, in normal subjects and patients with essential hypertension. In normal subjects, three components of renin release, "basal," "neural," and "sodium-sensitive," could be delineated. Among the hypertensive patients, abnormal patterns of renin release were noted. The categorization of patients according to "plasma-renin status," however, differed with the conditions of testing, being dependent both on the pathophysiology of the essential hypertension and the character of the renin-releasing stimulus, specifically whether this stimulus elevated plasma-renin activity through a predominantly neural (upright posture) or non-neural mechanism (dietary sodium deprivation). Abnormal plasma-renin activity in essential hypertension resulted in part from disordered sympathetic nervous system function. Patients with mild hypertension and elevated plasma-renin activity exhibited increased neural stimulation of renin release, whereas in patients with low plasma-renin values, all three components of renin release, including the neural element, were diminished.
Determinants of baroreflex sensitivity in man.
To determine the relationship of BRS to age, ACI, TPRI, and MBP, 61 male subjects, 19 to 65 years of age, whose MBP ranged from 77 to 134 mm Hg, were investigated. Partial correlative analysis was used to hold individual variables constant so that the effect of each on a given BRS relationship could be observed. An independent and significant relationship was observed between BRS and age; BRS and ACI correlated significantly through the influence of age, TPRI, and MBP; BRS and TPRI did not correlate; a significant BRS-MBP relationship existed through the influence of ACI. It was concluded that TPRI was not directly related to BRS and that the relationship of MBP to BRS was dependent on the influence of ACI whereas age was independently related to BRS.
Borderline hypertension: significance and management.
Explore the source record for details and available documents.
Mild high-renin essential hypertension. Neurogenic human hypertension?
To determine whether the elevated plasma renin activity in some cases of mild essential hypertension expresses sympathetic-nervous-system over-activity, we compared indexes of sympathetic activity in 16 patients with mild high-renin essential hypertension, 15 hypertensive patients with normal plasma renin activity and 20 normal subjects. Patients with elevated activity exhibited a raised plasma norepinephrine concentration (P less than 0.05), a greater fall in cardiac output with cardiac beta-adrenergic blockade by intravenous propranolol (P less than 0.01), reduction in total peripheral vascular resistance with alpha-adrenergic blockade produced by intravenous phentolamine (P less than 0.01), and reduction to normal of blood pressure by "total" autonomic blockade (atropine, propranolol and phentolamine). On psychometric testing, patients with high-renin hypertension, but not those with normal plasma renin activity, exhibited suppressed hostility (P less than 0.01), a behavioral pattern linked to increased sympathetic activity. The hypertension in these patients with high renin activity is neurogenic and possibly psychosomatic in origin.
Effect of beta adrenoceptor antagonists on baroreceptor reflex sensitivity in hypertension.
High-pressure baroreceptor reflex sensitivity (BRS) was estimated by measuring the reflex heart rate response to pharmacologic elevation of blood pressure (phenylephrine, 150 to 200 microgram intravenously) in 18 patients with essential hypertension on two occasions: after a 4-wk placebo period and after 9 wk of incremental doses of oral timolol (20, 40, and 60 mg daily). On placebo, measurements were performed both before and after propranolol (0.2 mg/kg intravenously). The level of cardiac vagal inhibition, estimated by the heart rate change after atropine (0.04 mg/kg intravenously), was similar in placebo and on timolol, thereby permitting comparisons of BRS. BRS on placebo (before and after propranolol) correlated with BRS on timolol ( r = 0.87 and 0.90, p less than 0.001), attesting to the reproducibility of BRS measurements. BRS was unchanged by either short-term (propranolol) or long-term (timolol) beta adrenoceptor inhibition. Results were similar in responders (n = 10), whose mean arterial blood pressure on timolol fell by 10 mm Hg or more, and in nonresponders. The findings do not provide evidence for a change in gain of the baroreceptor reflex arc under conditions of short- or long-term beta adrenoceptor inhibition.
Borderline hypertension. An overview.
Borderline hypertension is widespread. Though the increased blood pressure appears to be innocent, and upon rest frequently returns to the normal range, signs of complex and profound alteration of the physiologic control of the circulation can already be found. The pathophysiology of borderline hypertension is of particular interest since it may reveal clues about the processes which initiate the hypertension rather than the consequences of the primary blood pressure elevation. Patients with borderline hypertension are at a higher risk of developing future sustained hypertension and its consequences. The risk, however, is not sufficient to justify treatment in all cases. Patients must be followed to observe blood pressure trends and treatment attempted in the selected minority which has the highest risk. The determination of risk is based on repeated measurements of blood pressure and on the assessment of risk factors for atherosclerosis and for future hypertension.
Patterns of neurogenic involvement in borderline and essential hypertension.
Explore the source record for details and available documents.
Agreement among three different indices of sympathetic nervous system activity in essential hypertension.
Although plasma norepinephrine concentration often is elevated in patients with essential hypertension, the relevance of this to the pathogenesis of the blood pressure elevation remains uncertain. If the high concentration of plasma norepinephrine truly indicates sympathetic nervous system overactivity, it should be accompanied by hemodynamic features suggestive of sympathetic cardiovascular stimulation. This proposition was tested, and in part confirmed, in a study performed on 21 patients who had mild essential hypertension and on 11 normal subjects. Among hypertensive patients, plasma norepinephrine concentration was related to cardiac function but not to the level of the blood pressure or to total peripheral vascular resistance. Plasma norepinephrine concentration correlated significantly with heart rate and cardiac preejection period index at rest and with changes in cardiac output, heart rate, and preejection period after cardiac beta-adrenergic blockade produced by propranolol, 0.2 mg/kg intravenously. Patients with an elevated plasma norepinephrine concentrations (9 of 21) showed features of sympathetic cardiac stimulation, manifested by an elevated mean cardiac index and heart rate at rest and by normalization of both after treatment with propranolol. Thus, substantial agreement existed among three commonly used indices of sympathetic nervous system activity--plasma norepinephrine concentration, general hemodynamics at rest, and the hemodynamic response to pharmacologic autonomic blockade.
Abnormalities of autonomic nervous control in borderline hypertension.
The systemic hemodynamic was investigated in 145 young male patients with borderline hypertension and 85 control subjects. Response of the cardiac output, stroke volume and the heart rate to sequential parasympathetic, beta-adrenergic and alpha-adrenergic blockade was used for assessment of the autonomic nervous tone. These investigations suggest that the apparently "innocent" minimal blood pressure elevation in borderline hypertension is associated with a number of physiologic abnormalities: The cardiac output, heart rate and stroke volume can be elevated. In all patients the peripheral resistance is abnormal. An abnormal distribution of plasma renin values is detectable. The plasma volume is decreased in a proportion of patients. A number of these abnormalities can be explained by a neurogenic mechanism. The elevation of the cardiac output is entirely neurogenic. In a substantial minority of patients, the elevation of peripheral resistance is attributable to increased sympathetic drive. Indirect evidence indicates that the plasma renin elevation in borderline hypertension may also be neurogenic. Hypothetically the decreased plasma volume may stem from sympathetic effects on postcapillary vessels, but at the present there is no experimental evidence of support this view. The change in autonomic function in borderline hypertension involves both the sympathetic and parasympathetic efferents. Increased sympathetic stimulation is coupled with decrease parasympathetic inhibition. This points toward abnormal integration of the autonomic control, presumably in the medulla oblongata. The mechanism of the autonomic abnormality is not fully elucidated. The role of baroreceptors requires further investigation. In some patients the altered autonomic integration appears to be related to psychosomatic mechanisms.
Suppression of sympathetic nervous function in low-renin essential hypertension.
Study of general haemodynamics in 15 patients with low-renin essential hypertension showed haemodynamic and pathophysiological heterogeneity. However, there was suppression of sympathetic nervous system function in all low-renin patients, regardless of haemodynamic pattern. Subnormal sympathetic nervous activity was manifested by a low normal mean plasma-noradrenaline concentration at rest, diminished noradrenaline responsiveness to postural stimulation, and a reduced blood-pressure response to the indirectly acting sympathomimetic amine tyramine. It is proposed that the syndrome of low-renin essential hypertension is of diverse aetiology, but with secondary sympathetic nervous system underactivity as a feature common to the various forms. The low plasma-renin activity is probably an expression of defective sympathetic nervous system stimulation of renin release.
High-renin essential hypertension: adrenergic cardiovascular correlates.
1. Patients with mild essential hypertension and elevated plasma renin activity, when compared with normal subjects and hypertensive subjects with normal plasma renin, demonstrated features of sympathetic nervous cardiovascular excitation, accompanied by a raised plasma noradrenaline concentration. 2. An elevated heart rate at rest, shortened cardiac pre-ejection period, and greater heart rate reduction with acute beta-adrenoreceptor blockade (intravenous propranolol) in high-renin essential hypertension were indicative of adrenergic cardiac excitation. An elevated total of peripheral vascular resistance at rest and a greater fall in peripheral resistance with alpha-adrenoreceptor blockade (intravenous phentolamine) suggested the existence of a neurogenic increase in arteriolar resistance. 3. Blood pressure was normalized by 'total' autonomic blockade (atropine plus propranolol plus phentolamine) in the hypertensive subjects with elevated plasma renin activity. 4. These findings suggest that in mild high-renin essential hypertension increased adrenergic drive to the heart and resistance vessels exists. The elevation of blood pressure is sustained predominantly by neurogenic mechanisms. The high plasma renin activity is seen as an expression of sympathetic nervous system overactivity.
Increased central blood volume: a poosible pathophysiological factor im mild low-renin essential hypertension.
1. Patients with mild low-renin hypertension characteristically have increased central blood volume. The total blood volume is normal; the larger central blood volume reflects a shift of the blood from peripheral to central (cardiopulmonary) segments of the capacity system. 2. A relationship between central blood volume and plasma renin activity is demonstrable during tilting in normal and hypertensive subjects. In thirteen indivicuals there was a strong correlation between the decrease of the central blood volume and the increase in plasma renin activity in response to 12 min of 35 degree head-up tilt. 3. We propose that the elevated central blood volume causes greater stretch of cardiopulmonary mechanoreceptors and this in turn depresses renin release in mild low-renin hypertension.
Relationship of age and blood pressure to baroreflex sensitivity and arterial compliance in man.
1. The relationship between baroreflex sensitivity (BRS) and arterial compliance index (ACI) has been investigated (a) in paired subjects matched in one instance for systolic blood pressure with differing ages, and (b) in another instance matched for age with differing systolic blood pressures. 2. There was a significant negative correlation between BRS and age and between ACI and age in the twelve systolic blood pressure-matched subjects. 3. A significant negative correlation of systolic blood pressure with both BRS and ACI was observed in the fourteen age-matched subjects. 4. Both BRS and ACI appear to decrease with increasing age and systolic blood pressure. This decrease in BRS is probably due at least in part to the observed reduction in arterial distensibility.