VASCULAR AND EXCRETORY EFFECTS OF ANGIOTENSIN-II IN THE RAT ISOLATED-PERFUSED KIDNEY - INFLUENCE OF AN AT(1) AND A NONSELECTIVE AT RECEPTORANTAGONIST

Angiotensin II (AII) is a potent vasoconstrictor which, at physiologic al plasma concentrations, produces antinatriuresis, whereas high intra renal concentrations cause natriuresis and diuresis. We examined the e ffects of a selective AT(1) receptor antagonist, losartan, and a nonse lective AT receptor antagonist, Sar(1)Thr(8)AII, on the response to in fusion of AII in the isolated rat kidney perfused at constant pressure with a recirculating modified Krebs-Henseleit buffer. AII increased r enal vascular resistance (RVR), glomerular filtration rate (GFR) and u rinary volume (UV) and sodium excretion (UNaV) without changing the fr actional excretion of water or electrolytes. Thus, changes in GFR can account for the natriuresis/diuresis. Both AII receptor antagonists pr evented the increase in RVR. However, losartan was without effect on a ngiotensin-induced increases in GFR, UV or UNaV, whereas Sar(1)Thr(8) AII also prevented the increases in GFR, UV and UNaV. The angiotensin receptor mediating the increase in GFR can be dissociated from that me diating the increase in RVR, providing functional evidence of angioten sin receptor subtypes in the rat kidney.