Mode of action of beta-adrenergic blocking drugs in hypertension

Although they have been in use for over 20 years, the antihypertensive mode of action of beta-blocking drugs remains a matter for debate. Blood pressure falls with beta-blockers that have beta 1-selectivity, intrinsic sympathomimetic activity and membrane activity, but not those with a high level of pure beta-stimulation. Several suggestions have been made to explain this effect; a direct action on the central nervous system, adrenergic neurone blocking, perhaps via pre-synaptic beta 2-receptors, anti-renin activity, an increase of vasodilator prostaglandins, effects secondary to reduced cardiac output, and resetting of baroreceptors secondary to reduced pressor peaks to various pressor stimuli from the reduction in cardiac activity consequent to beta-blockade. There are also beta-blocking drugs which additionally have direct action to reduce peripheral resistance, via beta 2-mediated vasodilation, an alpha-blocking action or a direct vasodilator activity. Most attention has been given to a possible correlation to the effect of beta-adrenoceptor blocking drugs on the blood pressure and renin levels. Several investigations have found patients with high renin levels respond best, normal renin patients respond less well and low renin patients relatively poorly. However, others have not found a clear relationship.