Influence of Angiotensin Antagonists on Renal Vascular Resistance and Prostaglandin E Release

Abstract

Blood pressure (BP), renal arterial pressure and renal blood flow (RBF) were measured and blood samples were removed for determination of prostaglandin E (PGE) content in pentobarbital anesthetized dogs. Analysis of PGE with prior column separation was by radioimmunoassay utilizing a PGF antiserum and PGE specific antiserum. The angiotensin antagonists 1-Sar-8-Ala-angiotensin II (saralasin) and 1-Sar-Ileu-angiotensin II (1-S-8-I A) were infused intraarterially to the kidney achieving concentrations of 20 and 50-60 ng/ml and 10 and 20 ng/ml, respectively before and during partial occlusion of the renal artery (RAO). 1-S-8-I A, 20 ng/ml, caused a small increase in renal vascular resistance (RVR) before RAO, but saralasin exerted no effect prior to RAO. Arterial and renal venous PGE levels were not affected by the antagonists. RAO caused a decrease in RVR and gradual increase in BP which ranged from 29-38% and 12-15 mmHg, respectively at the 20 min interval. The concentration of PGE in renal venous blood was found to be increased and the AV difference was significant when measurements were made using PGF antiserum, but no change was detectable when using PGE antiserum. The infusion of saralasin, but not 1-S-8-I A in the above concentrations caused a significant decrease in RVR during RAO; however, no changes in PGE levels were obtained with either agent. These results indicate that 1-S-8-I A has a more potent agonistic renal vasoconstrictor effect than saralasin as found before RAO, and saralasin exerts a renal vasodilator action only during RAO, which is due to angiotensin antagonism and not to PGE release.