Is β1-antagonism essential for the antihypertensive action of β-blockers?

Abstract

Both nonselective β-blockers and β1-selective blockers are effective antihypertensive agents. β1-Blockade generally is considered to be responsible for their antihypertensive action, whereas β2-blockade is regarded as undesirable. These common assumptions notwithstanding, the mechanism by which β-blockers lower blood pressure remains unknown. To examine the possibility that β2-blockade may contribute to the antihypertensive action of β-blocker therapy, we studied the cardiovascular effects of compound ICI 118551, a β2-selective blocker. First, we showed that 50 mg t.i.d. orally is a β2-selective dose. In contrast to propranolol, 80 mg t.i.d., or atenolol, 100 mg once a day, 50 mg of ICI 118551 t.i.d. failed to block β1-mediated inotropic stimulation and stimulation of renin by isoproterenol. We then performed a double-blind, placebo-controlled trial in patients with mild essential hypertension to compare this compound with propranolol, 80 mg t.i.d., and showed that ICI 118551 significantly decreased systolic and diastolic blood pressure. This antihypertensive effect was demonstrated by direct as well as by indirect blood pressure measurements. Thus, contrary to prevailing thought, β2-blockade has an antihypertensive effect independent of, and distinct from, β1-blockade.