RENAL PHARMACOLOGY OF GR138950, A NOVEL NONPEPTIDE ANGIOTENSIN AT(1) RECEPTOR ANTAGONIST

This paper describes the renal pharmacology of the novel, specific, no n-peptide angiotensin AT(1) receptor antagonist, GR138950 4-cyclopropy l-2-ethyl-1H-imidazole-5-carboxamide). When administered to anaestheti sed salt-replete dogs, GR138950 caused renal vasodilatation and signif icant increases in sodium and urine excretion. No change in glomerular filtration rate was observed indicating that the natriuresis was a co nsequence of inhibition of tubular sodium reabsorption. Qualitatively similar but less marked changes in renal function were observed in res ponse to the angiotensin converting enzyme inhibitor, captopril, altho ugh in contrast to GR138950, captopril also caused a small but signifi cant fall in mean blood pressure. Intra-renal artery infusion of exoge nous angiotensin II resulted in dose-related renal vasoconstriction an d decreases in urine excretion, sodium excretion, fractional excretion of sodium and glomerular filtration rate. These renal effects of angi otensin II were all markedly antagonised by GR138950. We conclude that GR138950 is an effective antagonist of the renal haemodynamic and exc retory actions of endogenous and exogenous angiotensin II.