Haemodynamic consequences of intrinsic sympathomimetic activity in relation to changes in plasma renin activity and noradrenaline during beta-blocker therapy for hypertension.

The acute and long-term haemodynamic effects of pindolol, practolol, alprenolol, oxprenolol, acebutolol, penbutolol, metoprolol, atenolol, propranolol and timolol in patients with uncomplicated hypertension as reported in the literature were analysed. The long-term effects of these beta-adrenoceptor antagonists on plasma renin activity and the concentration of noradrenaline in plasma were also reviewed. In spite of the many pharmacological and physicochemical differences the drugs appeared to have a hypotensive effect of approximately equal magnitude. The degree of cardiodepression and the suppression of plasma renin activity as exerted by the different beta-blockers were inversely correlated with their pharmacologically defined degree of intrinsic sympathomimetic activity (ISA). The increments in vascular resistance acutely after administration of a beta-blocker are proportional to the degree of cardiodepression, suggesting that increased vasoconstrictor nerve activity mediated through the baroreflex had prevented an acute fall in arterial pressure in response to a given fall in cardiac output. After long-term therapy the inverse correlation between changes in cardiac output and changes in vascular resistance is shifted to a lower level of vascular resistance. Plasma renin activity and vascular resistance are inversely correlated during long-term beta-blocker therapy for hypertension. Consequently, the fall in vascular resistance underlying the hypotensive effect of beta-blockers cannot be explained by suppression of plasma renin activity. Thus, cardiodepression and renin suppression are not essential for the hypotensive effect of beta-adrenoceptor antagonists. The accessibility of the central nervous system to the different beta-blockers neither determines the time of onset of blood pressure reduction nor the magnitude of this effect. If it is neither the blockade of postsynaptic beta-adrenoceptors in the heart or on juxtaglomerular cells, nor the blockade of central beta-receptors that can be held responsible for the blood pressure lowering efficacy of beta-adrenoceptor antagonists, one is left with the remaining possibility that blockade of presynaptic beta-receptors underlies the vasodilator and antihypertensive action of these drugs. Changes in the concentrations of noradrenaline in plasma are compatible with this supposition, provided that changes in clearance of noradrenaline from plasma are taken into account.