REGIONAL HEMODYNAMIC-EFFECTS OF CANDESARTAN CILEXETIL (TCV-116), AN ANGIOTENSIN-II AT(1)-RECEPTOR ANTAGONIST, IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS

The regional hemodynamic effects of candesartan cilexetil (TCV-116), a selective angiotensin II AT(1)-receptor antagonist, and enalapril, an angiotensin-converting enzyme inhibitor, were compared in conscious s pontaneously hypertensive rats (SHR). A 7-day repeated administration study was carried out. TCV-116 (1 mg/kg, p.o.) and enalapril (10 mg/kg , p.o.) reduced blood pressure to the same extent 5 hr after administr ation on the Ist and the 7th day. At these points, the cardiac index a nd organ or tissue blood flow were measured by the non-radioactive col ored dye-extraction microsphere technique. Repeated administration of TCV-116, and single and repeated administration of enalapril significa ntly increased renal blood flow without any changes in the cardiac ind ex. TCV-116 and enalapril also tended to increase splanchnic blood flo w following the Ist dose but not the 7th dose. No significant changes in blood flow were observed in the brain, heart, adrenal, skin and ske letal muscle. These results suggest that the antihypertensive effects of TCV-116 and enalapril are attributable to the systemic reduction of vascular resistance caused by the dilatation of blood vessels. These hemodynamic effects of TCV-116, like those of enalapril, may be benefi cial in the treatment of hypertension.