Effects of intravenous diltiazem on cardiocirculatory dynamics and cardiac output distribution in conscious spontaneously hypertensive rats

Abstract

The effects of the calcium channel blocker, diltiazem hydrochloride (DZ), on conscious, resting spontaneously hypertensive rats (SHR) were evaluated and compared with results from parallel studies on Wistar-Kyoto (WKY) controls. DZ was administered as a continuous, cumulative infusion at rates equal to 0.40, 2.00, and 10.00 mg/kg/h (each dose was administered for 15 min). Parallel volume infusion (saline) controls were simultaneously conducted using volume infusion rates identical to those used in DZ studies (0.015, 0.100, and 0.500 ml/min). Three hours prior to study, animals were instrumented under halothane anesthesia for measurement of left ventricular, arterial, and central venous pressures; heart rate and arterial blood gases; and for injection of radioactive microspheres and subsequent determination of cardiac output, regional blood flows, and cardiac output distribution. All data were collected at control (C) before initiation of infusion, and at the end of each 15-min infusion period in each animal. At C and compared with WKY, SHR had increased heart rate (392 vs. 280 beats/min), mean arterial pressure (155 vs. 100 mm Hg), left ventricular peak systolic pressure (200 vs. 132 mm Hg), and systemic vascular resistance (0.3 vs. 0.2 mm Hg/ml/min/kg), and reduced stroke volume (1.8 vs. 2.2 ml/beat/kg); but no difference in cardiac output, left ventricular end diastolic pressure, or central venous pressure was found. At C, SHR tended to have increased blood flow and reduced vascular resistance in the coronary circulation and increased vascular resistance in the cutaneous, renal, bronchial arterial, hepatic arterial, testicular, and cerebral circulations. Infusion of DZ increased cardiac output and stroke volume and decreased heart rate, left ventricular and arterial pressures, and systemic vascular resistance in SHR. Similar changes of substantially smaller magnitude were observed in WKY. DZ increased flow and reduced resistance in the coronary and skeletal muscle circulations of SHR to a greater extent than in WKY. DZ also normalized vascular resistance in previously elevated regions. These results suggest that acute intravenous infusion of DZ at doses ranging between 2 and 5 mg/kg is capable of normalizing cardiovascular hemodynamics and regional blood flow distribution in SHR.