Calcium channels and regulation of vascular tone in hypertension

Abstract

The intravenous injection of calcium antagonists produces a hypotensive effect more pronounced in hypertensive than in normotensive animals. In conscious rats, Ishii et al. [17] have observed that a similar decrease of blood pressure was evoked by nifedipine at doses much lower in SHR than in WKY. Knorr and Garthoff [22] have compared the activity of nitrendipine and hydralazine on the blood pressure of SHR and WKY. They have reported that the vasodilator hydralazine was equipotent in both strains, but that nitrendipine evoked a much lesser reduction of blood pressure in WKY than in SHR, an observation consistent with clinical studies in humans [21, 25] and confirmed with lacidipine and amlodipine [11]. Godfraind and colleagues [12, 26] have measured the tissular concentration of amlodipine and nisoldipine at dosages which significantly reduced blood pressure in hypertensive (SHR) rats, but did not change the blood pressure of normotensive (WKY) rats. As shown on Table 1, the tissular concentration of the drugs was similar in both strains. Together with other haemodynamic observations [14], these studies indicate that calcium antagonists have an activity profile different from classical arteriolar vasodilators. Indeed, it has been reported that during chronic administration of a calcium antagonist, the decrease of blood pressure is observed without modification of the cardiac frequency [31]. It has been shown that vascular smooth muscle from hypertensive animals are hypersensitive to vasoconstrictors [5, 6, 10, 14, 20, 27, 31].