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Earlier studies have shown that relaxation in response to several agents is impaired in arteries from spontaneously hypertensive rats (SHR). We had previously reported that SHR aortas present a delayed relaxation when first exposed for 35 minutes to a 100 mM KCl solution and then transferred into physiological solution. The first phase of relaxation appeared similar in SHR and Wistar-Kyoto rat arteries, but the second phase was markedly slowed down in SHR arteries, giving rise to a postcontraction tone. In this study, we found that this postcontraction tone could be demonstrated not only in the aorta but also in the mesenteric artery, was independent of the presence of endothelium, increased with the age of SHR, and disappeared progressively when arterial segments were submitted to successive cycles of KCI depolarization followed by reimmersion in physiological solution. Chronic treatment of SHR with nisoldipine at doses that blocked the development of hypertension and attenuated the concomitant hypertrophy of heart and aorta, or in vitro pretreatment of SHR arteries with nisoldipine, decreased the contractile force developed by arteries in response to KCI depolarization and normalized the subsequent relaxation. ['H](+)-PN200-110 binding studies on heart and brain homogenates indicated an increase in apparent Kd in nisoldipine-fed rats without significant change in Bmax. Binding data were compatible with the view that occupation of dihydropyridine receptors by nisoldipine after chronic oral administration was responsible for the modifications observed ex vivo in the mechanical activity of arteries. We conclude that the postcontraction tone of SHR arteries was mainly due to an abnormally prolonged activation of calcium channels after transfer of depolarized arteries into the physiological solution and that a labile or slowly releasable factor was probably involved in this phenomenon. We suggest that the antihypertensive action of nisoldipine might be related to the mechanisms involved in the suppression of the postcontraction tone as observed in vitro and that this mode of action could be more important than the vasodilating effect of this drug. (Circulation Research 1991;68:674-682) ihydropyridine calcium antagonists are now D established for the management of essential hypertension, but the mechanism of their therapeutic action still needs to be characterized.1-3 Because dihydropyridines are potent blockers of potential-operated calcium channels, it has been proposed that their antihypertensive effect could be related to vasodilation. However, unlike

In isolated vessels in vitro nimodipine inhibits spasms induced by depolarization independently of the vessel's origin. The spasms induced by spasmogenic agonists such as serotonin, catecholamines, histamine, thromboxane, or whole blood are inhibited only in the cerebral vessels and not in the peripheral vessels. In vivo, nimodipine inhibits cerebrovascular spasms and brain damage in acute and chronic animal experiments. In chronic studies on stroke-prone, spontaneously hypertensive rats, nimodipine prevents cerebral tissue damage and prolongs the survival time without affecting the high blood pressure. Nimodipine inhibits the transmembraneous calcium influx in the smooth muscle cells of the cerebral vessels and thus prevents cerebral hypoperfusion after spasmogenic stimulation. In chronic cerebrovascular stress nimodipine prevents harmful calcium overloading and thus ensures the integrity of the cerebral parenchyma.