Antihypertensive action of propranolol: Specific antirenin responses in high and normal renin forms of essential, renal, renovascular and malignant hypertension

Abstract

The antihypertensive effect of propranolol was evaluated in 96 patients with various forms of hypertension preclassified according to plasma renin activity considered in relation to urinary sodium excretion. In essential hypertension (no = 74) 74 percent of high-renin patients (14 of 19) exhibited striking blood pressure reductions and 66 percent of normal-renin patients (25 of 38) achieved diastolic pressures less than or equal to 95 mm Hg. In sharp contrast, propranolol was completely ineffective in 17 low-renin patients. In all 11 patients with unilateral renal artery or parenchymal disease propranolol also lowered blood pressure in proportion to control renin levels. The response was predictive of the antihypertensive benefit of surgery even in six “normal” renin patients. In eight patients with high-renin malignant hypertension, propranolol normalized renin, aldosterone and potassium levels and produced dramatic though often incomplete blood pressure correction. In one low-renin patient with the malignant syndrone propranolol was ineffective. Regardless of etiology, antihypertensive effectiveness of propranolol correlated with control renin levels and with the decrement in renin secretion. Thus, a simple biochemical measurement indexed against sodium excretion predicted antihypertensive drug responsiveness. These observations expose, for the first time, a role for renin in a major fraction of patients with essential hypertension. Renin-induced vasoconstriction appears to cause the hypertension in high renin and also in some normal renin patients in whom renin may be inappropriately high for sodium balance. The antihypertensive action of propranolol strikes at both vasoconstrictor and volume components of hypertension since inhibition of renin secretion naturally retards aldosterone secretion, thus preventing compensatory salt and water retention which often vitiates hypotensive therapy. Accordingly, propranolol added to either vasodilator or diuretic agents ought to improve hypotensive effect by curtailing reactive increases in renin and aldosterone: this should also reduce diuretic-induced potassium loss. Propranolol given alone may prove effective in a sizeable fraction of all hypertensive disorders and without inducing the dehydrated hyperreninemic state caused by diuretics. Therefore propranolol may prove to be an alternate first approach, except in lowrenin hypertensions where this type of therapy is ineffective and contraindicated.