Sympathetic responsiveness and antihypertensive effect of beta-receptor blockade in essential hypertension

Effect of propranolol on noradrenaline kinetics in patients with essential hypertension.

“…It is possible, but unproven, that inhibition of sympathetic cardiovascular reflexes is one component of the antihypertensive action of f8-adrenoceptor blockers. Standing in apparent contradiction to this evidence of inhibition of sympathetic reflexes is the effect of /3-adrenoceptor blockers on the plasma noradrenaline response to dynamic exercise, the rise in noradrenaline levels with exercise being accentuated by /8-adrenoceptor blockade (Distler et al, 1978). But interpretation here is complicated by the reduction in noradrenaline clearance with beta-blockade we describe.…”

“…If the clearance of noradrenaline is lowered, the plasma concentration will Clonidine lowered the noradrenaline spillover rate to below normal in hypertensive patients, to levels similar to those found in patients with idiopathic peripheral autonomic insufficiency, while propranolol had no statistically significant effect overall. (Distler et al, 1978;Jones et al, 1980). Removal of noradrenaline from plasma is achieved by neuronal uptake into sympathetic nerve endings, extraneuronal uptake by other tissues, such as vascular endothelium, and metabolic conversion by 0-methylation, oxidative deamination, and conjugation (Kopin, 1979).…”

“…The magnitude of the antihypertensive effect of /8-adrenergic receptor blockers in individual patients, particularly at low doses, does appear to be related to biochemical measures of sympathetic nervous function, such as the plasma noradrenaline concentration at rest De Champlain, 1977), and the noradrenaline responses to upright posture (Esler & Nestel, 1973;Foumer et al, 1976) and exercise (Distler et al, 1978). At full doses of /3-adrenergic blockers, however, these indices of sympathetic function either entirely fail to predict the therapeutic outcome, as we found here and have noted in other studies (Esler& Nestel, 1973;Esler, Zweifler, Randall & De Quattro, 1977), or, much as for plasma renin activity, have predictive power rather too low to be clinically useful.…”

“…An early report of a reduction in plasma noradrenaline values with long-term /8-adrenergic receptor blockade (Brecht et al, 1976) was not confirmed in subsequent studies (Anavekar et al, 1975;. f8-adrenergic receptor blocking drugs may, in fact, elevate plasma noradrenaline values in hypertensive patients (Distler et al, 1978;Jones etal., 1980).…”

Short-term systemic hemodynamic adaptation to beta-adrenergic inhibition with atenolol in hypertensive patients.

“…However, long-term treatment of hypertensive patients with atenolol is associated with elevated plasrna norepinephrine levels, indicating increased sympathetic nervous system activity, both at rest and after exercise. 18 The initial fall in cardiac output following the initiation of beta-inhibitor therapy, in addition to triggering the reflex adjustments in alpha-adrenergic vasoconstrictor tone, appears to result in other peripheral vascular adjustments that oppose vasoconstriction. There is insufficient evidence at the present time to suggest whether these hemodynamic adjustments are mediated neurally or humorally.…”