RENAL RESPONSES TO AT(1) BLOCKADE IN ANGIOTENSIN-II-INDUCED HYPERTENSIVE RATS

Previous studies have shown that uninephrectomized rats infused chroni cally with low doses of angiotensin II (Ang II) develop progressive hy pertension that is prevented by coadministration of losartan in the dr inking water. The present study was performed to contrast the effects of chronic and acute losartan treatment in reversing the Ang II-mediat ed actions on arterial pressure and renal function. Ang II was infused subcutaneously via osmotic minipumps (40 ng/min) for 13 days in two g roups (N = 10 and N = 6); one group also received losartan in the drin king water (30 mg/kg day) throughout this period. Untreated rats (N = 6) and rats (N = 6) receiving only losartan served as control groups. Ang II-infused rats had higher mean arterial pressures (153 +/- 7 vers us 107 +/- 3 mm Hg) and lower GFR (0.7 +/- 0.04 versus 0.98 +/- 0.06 m L/min.g) than Ang II-infused rats receiving losartan chronically. The Ang II-infused rats responded to acute doses of losartan (10 mg/kg) wi th progressive reductions in arterial pressure and significant increas es in cortical blood flow (34 +/- 12% increase), renal plasma flow, GF R, and sodium excretion; however, the increases in renal blood flow an d GFR were not sustained as systemic arterial pressure decreased. Beca use Ang II-infused rats receiving losartan chronically still exhibited decreases in RBF in response to a bolus dose of Ang II, further studi es evaluated the effects of acute losartan treatment in rats treated c hronically with losartan. Although arterial pressure decreased only sl ightly, demonstrating adequate systemic vascular blockade, there were still substantial and sustained increases in renal plasma flow, cortic al blood flow (20 +/- 4% increase), GFR, and sodium excretion. In summ ary, the modest responses to acute losartan in Ang II-infused rats ind icate that chronic Ang II infusions lead to alterations in renal funct ion that are only partially reversible by acute losartan treatment. In contrast, chronic treatment with losartan prevents the Ang II-induced decrease in GFR. The renal responses to acute losartan in the Ang II- infused rats treated chronically with losartan suggest that substantiv e intrarenal actions of Ang II can be maintained even when the systemi c vascular AT(1) receptors are effectively blocked.