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This Article Full Text Full Text (PDF) All Versions of this Article: 297/6/F1606    most recent 90743.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kopkan, L. Articles by Majid, D. S. A. PubMed PubMed Citation Articles by Kopkan, L. Articles by Majid, D. S. A.

Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats

¹Physiology, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana; ; ²Physiology and Biophysics, SUNY at Buffalo, Buffalo, New York; and ; ³Department for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Submitted December 12, 2008 ; accepted in final form September 16, 2009

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 µg·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 µg·min^–1·100 g^–1], 17 ± 3% in urine flow (b, 10.6 ± 0.9 µg·min^–1·100 g^–1), 29 ± 3% in sodium excretion (b, 0.96 ± 0.05 µmol·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 µg·min^–1·100 g^–1; n = 6). In rats pretreated with superoxide (O₂^–) scavenger tempol (50 µg·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 µg·min^–1·100 g^–1; n = 6) but remained unchanged in amiloride-pretreated rats (0.2 µg·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.

cholesterol; nitric oxide; superoxide; epithelial Na⁺ channel; Na⁺/K⁺/2Cl^– cotransport; renal hemodynamics; sodium excretion