Systemic haemodynamics of dihydropyridine derivatives in conscious pigs with or without propranolol

The systemic haemodynamic effects of a 10 min i.v. infusion of three dihydropyridine Ca²⁺ channel blockers, nifedipine (1, 2 and 4 micrograms.kg^-1.min^-1), nisoldipine (0.5, 1 and 2 micrograms.kg^-1.min^-1) and nimodipine (1, 2 and 4 micrograms.kg^-1.min^-1) were studied in instrumented conscious pigs with or without a propranolol-induced beta-adrenoceptor blockade (0.5 mg.kg^-1 bolus followed by 0.5 mg.kg^-1.h^-1). Initial experiments showed that the solvent used for the Ca²⁺ channel blockers had no haemodynamic effects and that the effects of propranolol wer constant during a 30 min period. Nisoldipine, nimodipine and nifedipine elicited qualitatively similar effects, causing a dose-dependent decrease in blood pressure and systemic vascular resistance. These effects were accompanied by a reflex-mediated increase in heart rate, cardiac output and left ventricular rate of rise in pressure (LVdP/dt_max). Nisoldipine was about 2-3 times more potent than the other two drugs. Propranolol did not modify the vasodilation induced by the Ca²⁺ channel blockers but attenuated the increase in heart rate, cardiac output and LVdP/dt_max. In view of the reflex-tachycardia and the absence of negative inotropic actions, these Ca²⁺ channel blockers can be combined with beta-adrenoceptor antagonists without further compromising the left ventricular pump function.