Antiischemic Effects of Nifedipine in Isolated Working Heart Preparations of Healthy, Diabetic, and Hypertensive Rats

Abstract

We evaluated the antiischemic effects of nifedipine in isolated working rat hearts from age-matched normotensive Wistar-Kyoto rats (WKY), diabetic WKY, spontaneously hypertensive rats (SHR), and diabetic SHR. Diabetes was induced by streptozotocin. First, we constructed concentration-response curves for the negative inotropic effect of nifedipine in every group. After 15 min of pretreatment with nifedipine (EC60), low-flow ischemia (30 min) was induced by reducing the afterload from 51.5 to 11.0 mm Hg and nifedipine was infused simultaneously. The six measured parameters were left ventricular pressure (LVP), maximum rate of pressure increase (+dP/dtmax), maximum rate of pressure decrease (-dP/dtmax), aortic output (AO), coronary flow (CF), and cardiac output (CO), determined after 15-min equilibration in the working heart mode and at the end of the experiment. From these data, the recovery percentages were calculated. There were no significant differences in sensitivity to nifedipine (as measured by the EC50 concentration) between the four groups with respect to LVP, +dP/dtmax, -dP/dtmax, CF, and CO. However, hearts from SHR were less sensitive to nifedipine than those from diabetic SHR and nondiabetic WKY with regard to AO. In isolated hearts from nondiabetic WKY and SHR, there were no significant differences between vehicle-treated organs and nifedipine-treated preparations. In hearts from diabetic WKY and diabetic SHR, however, the nifedipine-treated group (LVP 87.1 +/- 3.3 and 60.5 +/- 12.1%, respectively) recovered significantly (p < 0.05) better from ischemia as compared with the control group (LVP 35.7 +/- 14.7 and 10.7 +/- 9.8%, respectively) (n = 6 for each group).(ABSTRACT TRUNCATED AT 250 WORDS)