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

Abstract

We showed recently that post-frusemide (furosemide) natriuresis was associated with a major depression of medullary circulation. In the present study, prior to administration of frusemide the tubular transport of NaCI was modified by loading the animals with 5% saline to elucidate a possible interrelation between the tubular and vascular effects of the drug. Moreover, a possible involvement of the renin-angiotensin system was examined by pharmacological blockade using captopril, an inhibitor of angiotensin converting enzyme (1 mg kg-1, I.V.), or losartan, a selective inhibitor of angiotensin AT1 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 cortical 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%) significantly more than the cortical flow (10.1 ± 1.0%; P < 0.001). The difference between the medulla and cortex was not significant in rats which showed high UNaV after hypertonic saline loading (2.0 ± 0.4 vs. 0.4 ± 0.1 μmol min-1 in non-loaded rats): 21.1 ± 3.9% and 15.8 ± 1.5%, respectively. At very high UNaV (9.5 ± 1.1 μmol min-1) the post-frusemide decrease in blood flow tended to be smaller in the medulla (7.6 ± 7.7%) than in the cortex (16.2 ± 2.6%). The fall in medullary blood flow was attenuated by pre-treatment with captopril (22.0 ± 3.3%) and abolished by pre-treatment with losartan (2.8 ± 11.8%). The decrease in cortical blood flow was not changed by hypertonic saline or angiotensin II blockers. The abolition of the post-frusemide depression of medullary blood flow by previous salt loading confirms the proposed link between tubular transport status and vasoconstriction. A similar modification of the response by blockade of the renin-angiotensin system suggests that the system is involved in the mechanism of medullary vasoconstriction.