Renal vascular effects of frusemide in the rat: influence of salt loading and the role of angiotensin II

We showed recently that post-frusemide (furosemide) natriuresis was associa ted with a major depression of medullary circulation. In the present study, prior to administration of frusemide the tubular transport of NaCl was mod ified by loading the animals with 5% saline to elucidate a possible interre lation between the tubular and vascular effects of the drug. Moreover, a po ssible involvement of the renin-angiotensin system was examined by pharmaco logical blockade using captopril, an inhibitor of angiotensin converting en zyme (1 mg kg(-1), i.v.), or losartan, a selective inhibitor of angiotensin AT(I) receptor (10 mg kg(-1), i.v.). The effects of frusemide (0.25 mg kg( -1) i.v., then the same dose given over 1 h) on renal medullary and cortica l circulation (using laser-Doppler flowmetry) and renal excretion of sodium (UNaV), water and total solutes were measured in anaesthetised rats. With no pre-treatment, frusemide decreased the medullary flow (36.6 +/- 6.0%) si gnificantly more than the cortical flow (10.1 +/- 1.0 %; P < 0.001). The di fference between the medulla and cortex was not significant in rats which s howed high UNaV after hypertonic saline loading (2.0 +/- 0.4 vs. 0.4 +/- 0. 1 mu mol min(-1) in non-loaded rats): 21.1 +/- 3.9% and 15.8 +/- 1.5%, resp ectively. At very high UNaV (9.5 +/- 1.1 mu mol min(-1)) the post-frusemide decrease in blood flow tended to he smaller in the medulla (7.6 +/- 7.7%) than in the cortex (16.2 +/- 2.6%). The fall in medullary blood flow was at tenuated by pre-treatment with captopril (22.0 +/- 3.3%) and abolished by p re-treatment with losartan (2.8 +/- 11.8%). The decrease in cortical blood flow was not changed by hypertonic saline or angiotensin II blockers. The a bolition of the post-frusemide depression of medullary blood flow by previo us salt loading confirms the proposed link between tubular transport status and vasoconstriction. A similar modification of the response by blockade o f the renin-angiotensin system suggests that the system is involved in the mechanism of medullary vasoconstriction.