The experimental use of calcium antagonists in the treatment of arterial hypertension.

The role of calcium for the function of vascular smooth muscle in the spontaneously hypertensive rat (SHR) was investigated, employing calcium blockers as a pharmacological tool. In the aorta of the SHR there was evidence for an increased dependency on extracellular calcium as the diseased vessels exhibited a faster membranal turn-over of calcium than vessels from normotensive control rats. In accordance with that, the effect of nifedipine appeared to be stronger in SHR vessels than in the normotensive one. Long-term treatment of SHRs with verapamil caused significant blood pressure reductions and regression of cardiac hypertrophy. In pilot studies in man both verapamil and nifedipine proved effective in lowering blood pressure. Nifedipine appeared the better suited. Hypertensive patients responded with a dose-related drop in blood pressure 10-30 min after the sublingual administration of nifedipine whereas normotensive subjects hardly showed any change of blood pressure. Following the acute administration of nifedipine a reflex increment of sympathetic tone was seen as reflected by increase in heart rate, circulating noradrenaline and plasma renin activity. An acute diuretic and natriuretic effect was seen together with a rise in urinary uric acid excretion. During long-term therapy nifedipine was effective in lowering blood pressure but side effects were common during monotherapy. When combined with a beta-adrenoceptor blocking agent side effects were few but concomitant diuretic therapy was often necessary.