EFFECTS OF NIFEDIPINE ON TOTAL CARDIAC-OUTPUT DISTRIBUTION IN CONSCIOUS RAT

Abstract

The effects of the Ca channel blocker nifedipine (NF) on cardiocirculatory dynamics and the total distribution of cardiac output in the conscious rats rat preparation were determined. Animals were instrumented for right atrial, left ventricular, arterial and venous pressure recordings and the radioactive microsphere technique was used to measure regional blood flow and cardiac output before (control) and during the i.v. infusion of either NF at 3 dosage levels [0.1, 0.6 and 1.5 mg/(kg .cntdot. h)] or vehicle (ethyl alcohol and polyethylene glycol) at rates matching those of the NF protocol [0.015, 0.1 and 0.5 ml/min]. The maximum rate of infusion represented approximately a 2% increase in blood volume/min. Systemic vascular resistance, stroke volume, regional vascular resistances and the regional percentage of distribution of total cardiac output were calculated. In the experimental group (n = 7), NF at the highest dosage level lowered mean arterial pressure by 20% and resulted in a significantly lower systemic vascular resistance and left ventricular end diastolic pressure compared with the parallel vehicle control data. The parallel vehicle only slightly but significantly lowered heart rate. The most predominant circulatory effect of NF was a significant 64% reduction in coronary vascular resistance also reflected in a substantial increase in coronary blood flow. NF also dilated the hepatic arterial circulation. The net effects of NF on cardiac output distribution involved a significant fractional shift away from the cutaneous and splenic circulatory beds in favor of the coronary, hepatic arterial and gastrointestinal circulations. Changes in the fractional distribution of cardiac output to the coronary, cutaneous and splenic beds dominated. The hemodynamic findings suggest that NF may have a substantial negative inotropic effect in the conscious rat. Circulatory data indicated that NF causes substantial changes in cardiac output distribution which may be partially supported by reflex baroreceptor-mediated sympathetic activity.