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.