Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

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

Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by... 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. renal blood flow; superficial blood flow; candesartan; decapsulation; tubular pressure; NKCC1 knockout Address for reprint requests and other correspondence: J. Schnermann, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 10, Rm. 4D51, 10 Center Drive-MSC 1370, Bethesda, MD 20892 (e-mail: jurgens@intra.niddk.nih.gov ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Renal Physiology The American Physiological Society

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

Download PDF
10 pages

Loading next page...
 
/lp/the-american-physiological-society/vasodilatation-of-afferent-arterioles-and-paradoxical-increase-of-UXghIGHyV0

References (49)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6127
eISSN
1522-1466
DOI
10.1152/ajprenal.00073.2007
pmid
17494095
Publisher site
See Article on Publisher Site

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. renal blood flow; superficial blood flow; candesartan; decapsulation; tubular pressure; NKCC1 knockout Address for reprint requests and other correspondence: J. Schnermann, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 10, Rm. 4D51, 10 Center Drive-MSC 1370, Bethesda, MD 20892 (e-mail: jurgens@intra.niddk.nih.gov )

Journal

AJP - Renal Physiology – The American Physiological Society

Published: Jul 1, 2007

There are no references for this article.