LOSARTAN ATTENUATES MODEST BUT NOT STRONG RENAL VASOCONSTRICTION INDUCED BY NITRIC-OXIDE INHIBITION

Previous studies showed variable success of angiotensin II (ANG II) an tagonists to oppose systemic and renal vasoconstriction during long-te rm nitric oxide synthase (NOS) inhibition. We explored in short-term e xperiments whether the systemic and renal vasodilatory response to ang iotensin II type 1 (AT(1))-receptor blockade depends on the extent of NOS blockade. In the first series of experiments, anesthetized rats un derwent clearance studies during continuous monitoring of mean arteria l pressure (MAP), renal blood flow (RBE flow probe), and renal vascula r resistance (RVR). Compared with control animals, low-dose infusion o f the NOS-inhibitor nitro-L-arginine (NLA) increased MAP and RVR, decr eased glomerular filtration rate, RBE and sodium excretion, and had no effect on plasma and kidney ANG II content. High-dose NLA induced str onger effects, did not affect plasma ANC II, and reduced kidney ANG II to similar to 60%. In the second series of experiments, we studied th e effect of low- and high-dose NLA on autoregulation of RBF. NLA induc ed a dose-dependent increase in MAP and decrease in RBF but left autor egulation intact. The AT(1)-receptor antagonist losartan restored MAP and RBF during low-dose NLA but had no depressor or renal vasodilating effect during high-dose NLA. In summary, short-term NOS blockade caus es a dose-dependent presser and renal vasoconstrictor response, withou t affecting renal autoregulation, and AT1-receptor blockade restores s ystemic presser and renal vasoconstrictive effects of mild NOS inhibit ion but fails to exert vasorelaxation during strong NOS blockade. Both levels of NOS inhibition did not importantly alter intrarenal ANG II levels. Apparently the functional role of endogenous ANG II as determi nant of vascular tone is diminished during strong NOS inhibition.