The effect of saralasin in the chronically cannulated ewe in the early puerperium.

The effects of angiotensin II receptor blockade with saralasin ((sar1) (ala8) angiotensin II) have been studied 1-3 days post partum in seven ewes with indwelling vascular cannulae. Control experiments were performed 48 h later in five of the same ewes. The infusion of saralasin at 1, 2, 4 and 8 micrograms kg-1 min-1 resulted in an initial small pressor response, followed by a depressor effect. A significant inverse correlation was demonstrated between log10 dose saralasin and the evoked change in diastolic blood pressure (r = -0.5891, P less than 0.005). A small and inconsistent depressor effect was found in the control experiments; there was no evidence for an association between dose and response (r = +0.0411, P greater than 0.85). These data were compared with those from a previously published study in which an identical infusion protocol for saralasin was used in ten chronically cannulated pregnant ewes. The slopes of the two dose-response curves were very similar (-14.9 +/- 4.3 post partum compared with -14.2 +/- 4.2) in the two groups. However, the average response was greater in the pregnant group, by 7.6 +/- 1.2 mmHg (P less than 0.005). Plasma renin concentration rose significantly during saralasin infusion (P less than 0.05) but was unchanged in control experiments, indicating blockade of the renin-angiotensin system by the removal of negative feed-back control by angiotensin II. Saralasin is known to exert an agonist effect when angiotensin II itself is not directly concerned in the regulation of arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)