Changes in adrenergic pressor responses by calcium channel modulation in conscious dogs

Abstract

The influence of the slow channel calcium entry blocker, nifedipine, and the slow channel calcium entry promoter, BAY-K 8644, on receptor-mediated hemodynamic responses was studied in chronically instrumented, conscious dogs. Following ganglionic, cholinergic, and beta-adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg iv), a selective alpha 1-adrenoceptor agonist, and B-HT 933 (20 micrograms/kg iv), a selective alpha 2-adrenoceptor agonist, as well as a nonadrenergic vasoconstrictor, vasopressin (0.003 IU/kg) were administered before and after infusions of nifedipine or BAY-K 8644 (0.25, 0.5, 1.0, and 2.0 micrograms X kg-1 X min-1). In doses producing minimal or no haemodynamic effects, nifedipine caused dose-related attenuation from control of phenylephrine- (from 26 +/- 3 to 8 +/- 1 mmHg), B-HT 933- (from 30 +/- 2 to 5 +/- 2 mmHg), and vasopressin- (24 +/- 1 to 2 +/- 2 mmHg) mediated changes in mean arterial pressure. In contrast, BAY-K 8644 produced dose-related potentiation from control of the same pressor responses (phenylephrine, 24 +/- 2 to 41 +/- 3 mmHg; B-HT 933, 28 +/- 3 to 46 +/- 2 mmHg; vasopressin, 25 +/- 3 to 45 +/- 5 mmHg). In addition, BAY-K 8644 produced a marked increase in the duration of the pressor response produced by all three agonists. Thus, in conscious dogs, alpha 1-, alpha 2-, and vasopressin-mediated pressor responses are strongly modulated by transmembrane calcium flux and can be influenced by dihydropyridine slow channel calcium agonists and antagonists.