Low-dose diuretic and beta adrenoceptor blocker in essential hypertension

The combination of hydrochlorothiazide (50 mg daily) and metoprolol (100 to 400 mg daily) reduced erect systolic blood pressure by 23.8 ± 4.0 (SE) mm Hg and erect diastolic pressure by 15.6 ± 2.2 mm Hg in 20 patients with essential hypertension. These decreases were of at least the same magnitude as the sum of the decrements induced by these drugs given separately. The rise in plasma renin activity (PRA) of 5.9 ± 1.2 ng/ml/hr induced by hydrochlorothiazide alone was reversed (p < 0.01) by the addition of metoprolol to control levels. Since hypokalemia can stimulate renin release, the absence of decreases in plasma potassium during combination treatment may have enhanced this renin-lowering effect. These findings appear to emphasize the importance of using relatively small doses of diuretics in combination treatment of hypertension; this approach avoided the countervailing effects of hyperstimulation of the renin-angiotensin system reported previously, which are not adequately controlled by concurrent β-blocker treatment. The control PRA tended to be predictive of the response to monotherapy, for it correlated directly (r = 0.52) with changes in diastolic blood pressure induced by hydrochlorothiazide alone and indirectly (r = −0.48) with those induced by metoprolol alone. The algebraic difference between the diastolic pressure decrements induced by metoprolol and hydrochlorothiazide within each patient also correlated with control renin (r = 0.61, p < 0.01), suggesting that the β-blocker is more effective in high-renin patients and that diuretics work best when renin is low. Black patients had larger decreases in blood pressure than whites on diuretic-alone. Clinical Pharmacology and Therapeutics (1980) 28, 149–158; doi:10.1038/clpt.1980.144