Comparison between the effects of MDL 72567 and nifedipine on various cardiovascular parameters in conscious sinoaortic-denervated rats and sham-operated controls.

In this study the effects of a new calcium entry blocking agent, 2,6-dimethyl-3-methoxycarbonyl-4-(2-nitrophenyl)-5-(2-furoyl)-1, 4-dihydropyridine (MDL 72567), were compared with those of nifedipine on blood pressure, heart rate, ECG, and cardiac contractility indices in conscious sinoaortic baroreceptor-denervated (SA-denervated) rats and their sham-operated controls. In sham-operated rats, the calcium-entry blocking agents (0.1-2 mg/kg i.v.) produced equivalent falls in blood pressure. However, nifedipine caused a much greater reflex tachycardia which was accompanied by a negative inotropic effect, and with the highest dose (2 mg/kg), a prolongation of the PQ interval. MDL 72567 induced an increase in myocardial contractility. In SA-denervated rats, both drugs produced an enhanced fall in blood pressure accompanied by a negative inotropic effect. Nifedipine did not change heart rate in SA-denervated rats, whereas MDL 72567 caused bradycardia. Thus, in these experiments, MDL 72567 caused less reflex tachycardia for a given fall in blood pressure than nifedipine and was less likely to cause myocardial depression. These effects of MDL 72567 may represent valuable, clinically relevant advantages over nifedipine.