In vivo renal vascular and tubular function in experimental hypercholesterolemia

Ariel Feldstein, James D. Krier, Mint Hershman Sarafov, Amir Lerman, Patricia J.M. Best, Stephanie H. Wilson, Lilach O. Lerman

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Hypercholesterolemia (HC) is often associated with impaired peripheral and coronary vascular responses to endothelium-dependent vasodilators, which are probably due to low bioavailability of nitric oxide. To examine the effect of HC on renal vascular and tubular function, 22 domestic pigs were studied after being fed a 12-week normal (n = 11) or HC (n = 11) diet. Renal regional perfusion and intratubular contrast media concentration in each nephron segment (representing fluid reabsorption) were quantified in vivo with electron-beam computed tomography before and after a suprarenal infusion of either acetylcholine (6 pigs of each diet) or sodium nitroprusside (SNP; 5 pigs of each diet). An increase in cortical perfusion, observed in normal pigs with acetylcholine (+35±6%, P=0.002) and SNP (+12±4%, P=0.005), was blunted in the HC group (+8.8±4.0, P=0.01, and -4.6±4.0%, P=0.1, respectively, P=0.003 and P=0.005 compared with normal) as was an increase in medullary perfusion (+58±21 in normal versus +24± 11% in HC, P=0.04). A decrease in the intratubular contrast media concentration in the distal tubule and collecting duct of normal pigs was observed in all tubular segments (and was significantly enhanced in the proximal tubule and Henle's loop) in the HC group, which was associated with increased sodium excretion. The tubular and renalexcretory responses to SNP were similar between the groups. In conclusion, early experimental HC in the pig attenuates renal perfusion response to both endothelium-dependent and -independent vasodilators possibly because of decreased bioavailability or decreased vascular responsiveness to nitric oxide. This vascular impairment may play a role in maladjusted renovascular responses and contribute to renal damage in later stages of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)859-864
Number of pages6
JournalHypertension
Volume34
Issue number4 II
DOIs
StatePublished - Oct 1999

Keywords

  • Atherosclerosis
  • Blood flow
  • Hypercholesterolemia
  • Kidney
  • Renal function

ASJC Scopus subject areas

  • Internal Medicine

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