Systemic and regional hemodynamic actions of calcium entry blockers in conscious spontaneously hypertensive rats

In the present study we investigated systemic and regional hemodynamic effects of the calcium entry blockers nifedipine, verapamil and PY 108-068 in conscious SHR. For systemic hemodynamic studies the animals were instrumented with an electromagnetic flowprobe on the ascending aorta, whereas for regional hemodynamic studies miniaturized Doppler flowprobes were implanted on the superior mesenteric and left renal artery and on the abdominal aorta. All three drugs caused a dose-dependent fall in mean arterial pressure and total peripheral resistance. Nifedipine and PY 108-068 increased cardiac output and heart rate, whereas verapamil only did so at high doses. Administration of each calcium entry blocker caused a dose-dependent fall in skeletal muscle vascular resistance, with renal and mesenteric resistance remaining virtually unchanged. A similar effect was observed after the administration of nifedipine to normotensive WKY rats. Surgical elimination of sino-aortic baroreflexes caused a 10 fold increase in antihypertensive potency of the three drugs in SHR. Moreover, dilatation in these animals was uniform in all beds studied. The results indicate that the three calcium entry blockers used are essentially non-selective vasodilators but that baroreflex mechanisms prevent vasodilatation in the renal and mesenteric beds in intact animals.