Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

Oppermann, Mona and Hansen, Pernille B. and Castrop, Hayo and Schnermann, Jurgen (2007) Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 293 (1). F279-F287. ISSN 1931-857X, 1522-1466

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Abstract

Loop diuretics like furosemide have been shown to cause renal vasodilatation in dogs and humans, an effect thought to result from both a direct vascular dilator effect and from inhibition of tubuloglomerular feedback. In isolated perfused afferent arterioles preconstricted with angiotensin II or N-G-nitro-L-arginine methyl ester, furosemide caused a dose-dependent increase of vascular diameter, but it was without effect in vessels from NKCC1(-/-) mice suggesting that inhibition of NKCC1 mediates dilatation in afferent arterioles. In the intact kidney, however, furosemide (2 mg/kg iv) caused a 50.5 +/- 3% reduction of total renal blood flow (RBF) and a 27% reduction of superficial blood flow (SBF) accompanied by a marked and immediate increase of tubular pressure and volume. At 10 mg/kg, furosemide reduced RBF by 60.4 +/- 2%. Similarly, NKCC1(-/-) mice responded to furosemide with a 45.4% decrease of RBF and a 29% decrease of SBF. Decreases in RBF and SBF and increases of tubular pressure by furosemide were ameliorated by renal decapsulation. In addition, pretreatment with candesartan (2 mg/kg) or indomethacin (5 mg/kg) attenuated the reduction of RBF and peak urine flows caused by furosemide. Our data indicate that furosemide, despite its direct vasodilator potential in isolated afferent arterioles, causes a marked increase in flow resistance of the vascular bed of the intact mouse kidney. We suggest that generation of angiotensin II and/or a vasoconstrictor prostaglandin combined with compression of peritubular capillaries by the expanding tubular compartment are responsible for the reduction of RBF in vivo.

Item Type: Article
Uncontrolled Keywords: BLOOD-FLOW AUTOREGULATION; THICK ASCENDING LIMB; TUBULOGLOMERULAR FEEDBACK; MYOGENIC AUTOREGULATION; PROSTAGLANDIN SYSTEM; BARTTERS-SYNDROME; ARACHIDONIC-ACID; ANGIOTENSIN-II; LOOP DIURETICS; NITRIC-OXIDE; renal blood flow; superficial blood flow; candesartan; decapsulation; tubular pressure; NKCC1 knockout
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie
Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Dec 2020 11:30
Last Modified: 02 Dec 2020 11:30
URI: https://pred.uni-regensburg.de/id/eprint/32513

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