Converting enzyme inhibitor and saralasin infusion in rats. Evidence for an additional vasodepressor property of converting enzyme inhibitor.

Converting enzyme inhibitor (CEI) produced a greater fall in blood pressure (BP) than the competitive antagonist of angiotensin II, sarcosine-alanine angiotensin II (saralasin), when administered to saltdepleted rats; there was no difference in BP response in salt-loaded rats. Thus, two widely used methods of inhibiting the renin-angiotensin system give discrepant effects. The renin-angiotensin system was blocked in anesthetized rats by an infusion of saralasin, and then a bolus injection of CEI was given. A further significant fall in blood pressure occurred in salt-depleted rats ( -45 .7 ± 6.8 mm Hg; mean ± SE). There was only a small change in blood pressure of salt-loaded rats ( -11 .2 ± 3.1 mm Hg) and no change in blood pressure of salt-depleted rats 1 hour after bilateral nephrectomy. Saralasin infusion after CEI did not influence BP. Bradykinin infusion potentiated the depressor effect of CEI in bilaterally nephrectomized rats. Renin infusion restored the depressor response of nephrectomized rats to saralasin, but administration of CEI then caused no further fall in BP. BP of saralasin-infused rats with Goldblatt two-kidney hypertension given CEI fell by 11.1 ± 5 . 4 mm Hg; after dietetic salt depletion, BP fell by 20.5 ± 9.9 mm Hg with CEI. Bilateral nephrectomy abolished this response to CEI. Hence, CEI has a significant vasodepressor action in addition to inhibition of angiotensin II production. Since it can be restored in nephrectomized animals by bradykinin infusion, the component of the vasodepressor action of CEI which cannot be blocked by saralasin may be identical with its bradykinin-potentiating action. If so, changes in the renal kallikrein bradykinin system may have an important role in BP control in response to changes in sodium balance and in hypertension.