Both nonselective beta-blockers and beta 1-selective blockers are effective
antihypertensive agents. beta 1-Blockade generally is considered to be responsible for their
antihypertensive action, whereas beta 2-blockade is regarded as undesirable. These common assumptions notwithstanding, the mechanism by which beta-blockers lower blood pressure remains unknown. To examine the possibility that beta 2-blockade may contribute to the
antihypertensive action of beta-blocker
therapy, we studied the cardiovascular effects of compound
ICI 118551, a beta 2-selective blocker. First, we showed that 50 mg t.i.d. orally is a beta 2-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 beta 1-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, beta 2-blockade has an
antihypertensive effect independent of, and distinct from, beta 1-blockade.