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Biomedical subjects

M Esler

Publications and source records attributed to M Esler.

At least 109 records · Page 6Linked to original sources
PubMed1977

Sympathetic nerve hyperactivity in high-renin hypertension effects of saralasin infusion.

We found increased levels of catecholamines in some patients who had high-renin hypertension. To study relations between angiotensin and the sympathetic nerves further, we infused saralasin, a blocker of angiotensin II, into 11 hypertensive patients being evaluated for renovascular hypertension. There were variable responses of mean arterial pressure, plasma renin activity, and norepinephrine levels. When high-renin hypertensive patients with increased levels of norepinephrine were compared with those having high renin and normal levels of norepinephrine, they showed a lesser decrease in mean arterial pressure--5 +/- 5% versus 14 +/- 4%, P less than 0.05--a decrease in plasma renin activity of 20 +/- 17% versus an increase of 77 +/- 24% (P less than 0.01), and a decrease in norepinephrine levels of 42 +/- 7% versus an increase of 10 +/- 23% (P less than 0.05) (means +/- SE). The evidence suggests that patients with high-renin levels are heterogeneous and that the primary mediator of the hypertension is sympathetic tone hyperactivity in those with increased levels of norepinephrine and angiotensin excess in those with normal levels of norepinephrine.

Adolescent↗
PubMed1977

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.

Adolescent↗
PubMed1976

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.

Adult↗
PubMed1976

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.

Adolescent↗
PubMed1976

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.

Adult↗
PubMed1976

Sympathotonia in primary hypertension and in a caricature resembling dysautonomia.

1. Plasma catecholamines and adrenergic correlates of cardiac function were compared in young men with borderline hypetension, classified according to renin status (group 1). Plasma catecholamines were increased and cardiac pre-ejection periods were shortened in 'high'-renin patients. 2. Plasma catecholamines were raised in 70% of 'high'-renin patients with primary hypertension (group 2), were related directly with age in normotensive females and were related inversely with catecholamine responses to postural stress in both normotensive and hypertensive subject (P less than 0-01). 3. The raised catecholamines of four 'high'-renin patients with pronounced features of sympathetic nerve activity-acricatures were elevated further during,hypertensive periods. Mean arterial blood pressures were reduced 20-30% after either alpha- or beta-receptor blockade. Catecholamines were reduced after beta-receptor blockade. 4. There appears to be a spectrum of neurogenic 'gain' in primary hypertension; it is suppressed in 'low'-renin hypertension, directly related to blood pressure in 'normal'-renin hypertension, increased in 'high'-renin hypertension and achieves a maximum in caricatures. Neurogenic factors seem to be important in the cause and maintenance of 'high'- and 'normal'-renin hypertension respectively. The caricatures may be examples of a severe form of hypothalamic stimulation.

Adolescent↗
PubMed1976

Factors influencing the choice of antihypertensive agents.

Personal, social, and medical factors unique to individual patients have a bearing on the efficacy of specific antihypertensive agents and on the frequency and severity of side effects. The factors relate to age, sex, occupation, potential for adherence to a prescribed program of therapy, and associated health problems. The importance of a simple, inexpensive program is emphasized.

Age Factors↗
PubMed1976

Dissociation of the renin lowering and antihypertensive actions of propranolol.

Suppression of renin release by beta-adrenoceptor blocking drugs has been advocated as the prime blood pressure lowering mechanism of these agents. The present report casts doubt on this proposition in three ways. In the first study, involving 22 patients with borderline hypertension, patients with elevated plasma renin levels showed normalization of the blood pressure after pharmacological autonomic blockade with intravenous atropine, propranolol and phentolamine, the time course of the pressure fall being such as to exclude suppression of renin release as the antihypertensive mechanism. It is clear that in patients with mild hypertension and high plasma renin levels, the elevation of blood pressure is maintained by a neurogenic mechanism, the elevated plasma renin having no direct role in sustaining the higher blood pressure. In two additional studies involving 21 patients in all with mild to moderately severe essential hypertension, to whom propranolol was administereed by mouth for 1--3 months, two findings were of interest:1) patients with low-renin essential hypertension showed a good antihypertensive response to propranolol, and 2) in some patients a dosedependent dissociation of the renin and blood pressure lowering action of propranolol could be demonstrated. These findings militate against the assumption that propranolol selectively lowers the blood pressure in "renin-dependent" hypertension, and strongly suggest that the antihypertensive action of this drug is not mediated by depression of plasma renin activity.

Atropine↗
PubMed1975

Autonomic nervous cardiovascular regulation in borderline hypertension.

Borderline hypertension attracts investigative interest since it is an early predictor of established hypertension and its sequelae. This condition offers the opportunity of studying arterial hypertension at its inception, before the development of secondary pressure-related changes. A number of abnormalities of the circulation have been described in borderline hypertension. The peripheral resistance is either elevated or inappropriately adjusted to the prevailing increased cardiac output and blood flow. Cardiac output, heart rate and stroke volume are elevated in a proportion of patients. Decreased plasma volume, enhanced pressor responsiveness and elevated plasma renin activity have also been noted. All these changes could hypothetically be explained by a neurogenic mechanism. Although the experimental evidence supporting a neurogenic origin of borderline hypertension is incomplete and often indirect, most findings point toward an abnormal autonomic control of the circulation in this disorder. It is postulated that in a subgroup of patients with borderline hypertension a neurogenic mechanism is in fact operative. There is a need for further characterization of this category of borderline hypertension and for description of its natural history, particularly in relation to the possible subsequent development of essential hypertension.

Autonomic Nervous System↗
PubMedDate not supplied

Non-invasive evaluation of the cardiac function in golden retriever dogs by radionuclide angiography.

Golden Retriever dogs manifest an X-linked, Duchenne-like, muscular dystrophy with a characteristic lack of dystrophin. Histologic findings have demonstrated the cardiac involvement in these dogs to be a model for the cardiac insufficiency in human Duchenne muscular dystrophy (DMD). The goal of this study was to assess the capability of radionuclide angiography (RNA) as an assessment tool to measure the ventricular dysfunction in these dogs. Three dogs, one normal and two with muscular dystrophy (MD), were studied by equilibrium gated blood pool. Red blood cells were labelled with 420 MBq of 99mTc. The three dogs lying on their left sides on the table, received no drugs and were not restrained in any manner. RNA left ejection fraction (EF) and echographic measurements of left ventricular fractional shortening (FS) were performed during the same session. EF values were 61%, 48%, 36% and FS values were 47%, 32%, 26%, respectively, for the control dog, the 6 month old MD dog and the 12 month old MD dog. This preliminary study demonstrates the potential usefulness of RNA for the non-invasive follow-up exams of specific therapy in a canine model of muscular dystrophy.

Animals↗
PubMedDate not supplied

Assessment of neuronal uptake of noradrenaline in humans: defective uptake in some patients with essential hypertension.

1. Disappearance of tritiated noradrenaline from plasma, after infusion to steady-state, was studied to assess neuronal uptake of noradrenaline inessential hypertension. 2. Plasma tritiated noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed both in normal subjects after desipramine, and in patients with sympathetic nerve dysfunction (autonomic insufficiency). 3. In nine of thirty-eight hypertensive patients the t1/12 similarly was prolonged. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, was increased in these patients. 4. Defective neuronal uptake of noradrenaline, by exposing adrenergic recepotors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.

Adult↗
PubMedDate not supplied

Differing noradrenaline kinetics in essential hypertension and depressive illness, two diseases in which the plasma concentration of noradrenaline is sometimes elevated.

1. The rate of spill-over of noradrenaline to plasma, and neuronal noradrenaline uptake, which influences spill-over, were studied in patients with essential hypertension and depressive illness. 2. Noradrenaline spill-over was increased in seven of thirty-four patients with essential hypertension and five of eleven patients with primary depressive illness, compared with values in seventeen normal subjects (range 1.0-3.63 nmol/min per m2). 3. Faulty neuronal reuptake of noradrenaline seemed to be the cause of higher noradrenaline spill-over in patients with essential hypertension. Increased sympathetic nerve firing rates apparently were responsible in the primary depressives, despite their normal blood pressure. 4. These puzzling findings suggest that hypertension occurs when neurotransmitter excess is due to defective noradrenaline reuptake (in essential hypertension), but not chronically increased nerve firing (in depressive illness).

Adult↗
PubMedDate not supplied

Norepinephrine kinetics in essential hypertension. Defective neuronal uptake of norepinephrine in some patients.

To assess sympathetic nervous system function in essential hypertension, we measured the rates of release to and removal from plasma of the sympathetic neurotransmitter, norepinephrine. In normal subjects, disappearance of tritiated l-norepinephrine from plasma, after infusion to steady state, was biexponential, with t1 1/2 = 2.0 +/- 0.4 minutes (mean +/- standard deviation) and t2 1/2 = 33 +/- 15 minutes. The rapid component of removal seemed to represent neuronal uptake of norepinephrine: the t1 1/2 was lengthened by the selective inhibitor of neuronal norepinephrine uptake, desipramine; it was not changed by the extraneuronal uptake blocker, cortisol; and it was prolonged in patients with peripheral sympathetic nerve dysfunction (idiopathic autonomic insufficiency). In eight of 37 hypertensive patients, the t1 1/2 was greater than 2.8 minutes (range, 3.3-6.0 min), longer than in any normal subject; this appears to be presumptive evidence of the existence of defective neuronal norepinephrine uptake. In these patients the rate of spillover of norepinephrine to plasma, of transmitter escaping uptake after release, was 0.73 +/- 0.39 micrograms/m2/min (4.3 +/- 2.3 nmoles/m2/min), higher than in normal subjects, 0.36 +/- 0.14 micrograms/m2/min (2.1 +/- 0.8 nmoles/m2/min) (p less than 0.01). A defect in neuronal uptake of norepinephrine, by exposing adrenergic receptors to high local norepinephrine concentration, may be important in the pathogenesis of blood pressure elevation in some patients with essential hypertension.

Adolescent↗
PubMedDate not supplied

Central nervous system monoamine neurotransmitter turnover in primary and obesity-related human hypertension.

Recent experiments in laboratory animals have challenged the conventional view that the dominant effect of CNS noradrenergic neurons in cardiovascular control is sympathetic nervous inhibition and blood pressure reduction, describing instead sympathetic activation. We have tested whether such a stimulant effect on sympathetic outflow is also evident in human hypertension. CNS norepinephrine turnover was estimated from the combined overflow of norepinephrine, MHPG and DHPG into the internal jugular veins. Cerebral blood flow scans allowed differentiation between cortical and subcortical jugular venous drainage. In patients with pure autonomic failure, jugular overflow of norepinephrine and metabolites was not reduced, indicating brain neurons and not cerebrovascular sympathetics was the source. In healthy men, CNS norepinephrine turnover and muscle sympathetic nerve activity were directly related (p < 0.02). Administration of the ganglion blocker, trimethaphan, caused a compensatory five-fold increase in jugular overflow of MHPG. Conversely, intravenous clonidine reduced CNS norepinephrine turnover by approximately 50%, this possibly representing a mechanism of drug action. In cardiac failure patients, sympathetic nervous activation was associated with a trebling of CNS norepinephrine turnover (p < 0.01). In untreated patients with essential hypertension, the sympathetic activation present was associated with 250% higher CNS norepinephrine turnover (p < 0.01), but in subcortical brain regions only. A close and direct relation exists between brain norepinephrine turnover and human sympathetic nervous activity. CNS release of norepinephrine, presumably in the forebrain where noradrenergic neurons are sympathoexcitatory and pressor, mediates increased sympathetic nerve firing in patients with essential hypertension.

Animals↗
PubMedDate not supplied

Modulation of vascular function by diet and exercise.

Clinical research is conducted in free living individuals who are always subject to the influences on vascular function and the major cardiovascular regulators of their lifestyle. The purpose of this paper is to review some lifestyle influences on cardiovascular function, particularly the sympathetic nervous system and endothelially mediated vasodilatation. There are highly differentiated sympathetic responses to feeding, and to acute exercise. Over a longer period obesity has a typical pattern of sympathetic activity. Reduced dietary salt intake elicits profound localised increases in sympathetic activity to the kidney. Marine oil supplementation attenuates the sympathetic responses to psychological stress and improves endothelially mediated vasodilatation in hypercholesterolaemics. Exercise training reduced total noradrenaline spillover, the major beds affected being the renal and skeletal muscle. These examples illustrate the dynamic nature of vascular dilatation and that, like the sympathetic nervous system, it is modulated by short, medium and long term influences. In both cases there is regulation both at a local and systemic level. Habitual, and recent, lifestyle can exert important cardiovascular effects which must be taken into account in clinical and epidemiological research.

Arginine↗