Antihypertensive effects of S9490-3, a new converting enzyme inhibitor, in the conscious spontaneously hypertensive rat.

ABSTRACT

The acute and chronic cardiovascular effects of S9490-3, a new converting enzyme inhibitor, were studied by means of a computerized analysis of the intra-aortic blood pressure recorded for 48 consecutive hours, in the conscious, unrestrained adult spontaneously hypertensive rat (SHR). The software used allowed the simultaneous study of one control and one treated animal. A single intravenous dose of S9490-3 (2 mg/kg) induced a rapid fall in systolic and diastolic blood pressure, which remained significant for 11 h. This decrease was not associated with an elevation in heart rate. A chronic oral treatment with S9490-3 (1 mg/kg/24 h for 12 days) significantly lowered systolic and diastolic blood pressure and reduced the variability of systolic blood pressure. The heart rate was slightly increased at rest (day time) but significantly elevated in the freely exercising SHR (night time). However, it must be noted that this increase remained moderate. The baroreflex sensitivity of chronically treated animals was enhanced when measured after phenylephrine but not after nitroglycerine bolus. Chronically given S9490-3 significantly reduced the pressor effect of phenylephrine and decreased the left ventricle weight.