Faculty Collaboration Database

Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats. Am J Physiol Renal Physiol 2009 Dec;297(6):F1606-13

Date

09/25/2009

Pubmed ID

19776170

Pubmed Central ID

PMC2801331

DOI

10.1152/ajprenal.90743.2008

Scopus ID

2-s2.0-71449088250 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Although hypercholesterolemia is implicated in the pathophysiology of many renal disorders as well as hypertension, its direct actions in the kidney are not yet clearly understood. In the present study, we evaluated renal responses to administration of cholesterol (8 microg x min(-1).100 g body wt(-1); bound by polyethylene glycol) into the renal artery of anesthetized male Sprague-Dawley rats. Total renal blood flow (RBF) was measured by a Transonic flow probe, and glomerular filtration rate (GFR) was determined by Inulin clearance. In control rats (n = 8), cholesterol induced reductions of 10 +/- 2% in RBF [baseline (b) 7.6 +/- 0.3 microg x min(-1).100 g(-1)], 17 +/- 3% in urine flow (b, 10.6 +/- 0.9 microg x min(-1).100 g(-1)), 29 +/- 3% in sodium excretion (b, 0.96 +/- 0.05 mumol.min(-1).100 g(-1)) and 24 +/- 2% in nitrite/nitrate excretion (b, 0.22 +/- 0.01 nmol.min(-1).100 g(-1)) without an appreciable change in GFR (b, 0.87 +/- 0.03 ml.min(-1).100 g(-1)). These renal vasoconstrictor and anti-natriuretic responses to cholesterol were absent in rats pretreated with nitric oxide (NO) synthase inhibitor, nitro-l-arginine methylester (0.5 microg x min(-1).100 g(-1); n = 6). In rats pretreated with superoxide (O(2)(-)) scavenger tempol (50 microg x min(-1).100 g(-1); n = 6), the cholesterol-induced renal responses remained mostly unchanged, although there was a slight attenuation in anti-natriuretic response. This anti-natriuretic response to cholesterol was abolished in furosemide-pretreated rats (0.3 microg x min(-1).100 g(-1); n = 6) but remained unchanged in amiloride-pretreated rats (0.2 microg x min(-1).100 g(-1); n = 5), indicating that Na(+)/K(+)/2Cl(-) cotransport is the dominant mediator of this effect. These data demonstrate that cholesterol-induced acute renal vasoconstrictor and antinatriuretic responses are mediated by a decrease in NO production. These data also indicate that tubular effect of cholesterol on sodium reabsorption is mediated by the furosemide sensitive Na(+)/K(+)/2Cl(-) cotransporter.

Author List

Kopkan L, Khan MA, Lis A, Awayda MS, Majid DS

MESH terms used to index this publication - Major topics in bold

Absorption
Animals
Antioxidants
Cholesterol
Cyclic N-Oxides
Drug Carriers
Enzyme Inhibitors
Furosemide
Hemodynamics
Infusions, Intra-Arterial
Kidney
Male
NG-Nitroarginine Methyl Ester
Natriuresis
Nitric Oxide
Nitric Oxide Synthase
Polyethylene Glycols
Rats
Rats, Sprague-Dawley
Renal Artery
Sodium-Potassium-Chloride Symporters
Spin Labels
Vasoconstriction