Protective Effects of Calcium Antagonists on Hypertensive Diseases in Heart, Brain, and Kidney of Hypertensive Rats

Abstract

The most evident result of calcium antagonist action in hypertension is the lowering of blood pressure. However, the protective effects of this type of agents on tissue structure and function may be largely independent of their vasorelaxant action. The natriuretic effect of dihydropyridine calcium antagonists is found in their antihypertensive dose range and was demonstrated to prevent volume expansion in (1-kidney, 1-clip)-hypertension. The functional recovery of the post-ischemic kidney was improved by treatment with nifedipine. With the help of biopsies of small mesenteric arteries of salt-loaded Dahl-S-rats with preexistent hypertension before arid after 6 weeks of nifedipine, the formation of new arterial endothelium and internal elastic lamina was observed. Morbidity, mortality, and incidence of organ lesions were largely reduced or prevented by the treatment of adult stroke-prone SHR with blood-pressure-neutral doses of nitrendipine or nimodipine. Nimodipine was shown largely to normalize brain and kidney calcium concentrations without altering serum ionized calcium concentration or blood pressure. It is concluded that the direct protective effects of calcium antagonists on cell structure and function might be therapeutically more important than their depressor effect.