Effects of Long-term Blockade of Angiotensin Converting Enzyme with Captopril (SQ14,225) on Hemodynamics and Circulating Blood Volume in SHR

Male spontaneously hypertensive rats (SHR), 13 weeks old, received oral administration of captopril (SQ14,225) daily at a dose of 10 mg/kg or 30 mg/kg; or water at 2 ml/kg, for 6 weeks. Captopril suppressed the development of hypertension slightly at the lower dose and completely at the higher dose. At 6 weeks of dosing, hemodynamic parameters were measured by the tracer microsphere method and blood volume by the dilution method using 51Cr erythrocytes. Cardiac output (CO) increased and mean blood pressure decreased in a dose-dependent manner; thus, total peripheral resistance decreased. Cerebral and renal blood flows increased in a dose-dependent manner while blood flow to other organs tended to increase or remained unchanged. There was no significant differences in the circulating blood volume among the three groups. In conclusion, long-term blockade of angiotensin converting enzyme (ACE) with captopril dilated blood vessels in the whole body, especially in the brain and kidney, and lowered blood pressure without causing plasma expansion or tachycardia.