Andreas Dr. Knorr

Protection Against Hypertensive Cardiovascular Damage by Dihydropyridine Calcium Antagonists

It is commonly acknowledged that calcium antagonists inhibit transmembrane calcium influx in arteriolar smooth muscle cells and thus reduce total peripheral resistance. This mechanism of action is supposed to be the prime basis of the antihypertensive action of these agents. However, despite their action as arteriolar vasodilators, therapeutically, calcium antagonists differ from vasodilators with other mechanisms of action (e.g., hydralazine or minoxidil) in having a marked natriuretic and diuretic action [6,8,17] and have been shown to preserve structure and function of heart, kidney, and mesenteric arterioles of hypertensive rats [2–4,10,13,18,24–26]. Therefore, tissue-protective effects of dihydropyridine calcium antagonists which might be unrelated to their hemodynamic actions, might add significantly to their long-term therapeutic efficacy in hypertension. We investigated the antihypertensive and tissue-protective effects of dihydropyridine calcium antagonists in long-term experiments: (1) nisoldipine in salt-loaded Dahl S and R rats in a preventive and therapeutic experiment, (2) nitrendipine in spontaneously hypertensive rats and Wistar-Kyoto rats in comparison to a classical vasodilator, and (3) nimodipine in stroke-prone spontaneously hypertensive rats in comparison to parathyroidectomy.