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/dtmax). 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/dtmax. 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.
Duncker
D J
DJ
Department of Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
Saxena
P R
PR
Verdouw
P D
PD
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D015737:Nisoldipine; D011433:Propranolol / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D015737:Nisoldipine; D009553:Nimodipine; D011433:Propranolol; D009543:Nifedipine