In vivo renal vascular and tubular function in experimental hypercholesterolemia

Hypercholesterolemia (HC) is often associated with impaired peripheral and coronary vascular responses to endothelium-dependent vasodilators, which ar e probably due to low bioavailability of nitric oxide. To examine the effec t of HC on renal vascular and tubular function, 22 domestic pigs were studi ed after being fed a 12-week normal (n=11) or HC (n=11) diet. Renal regiona l perfusion and intratubular contrast media concentration in each nephron s egment (representing fluid reabsorption) were quantified in vivo with elect ron-beam computed tomography before and after a suprarenal infusion of eith er 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 blu nted in the HC group (+8.8+/-4.0, P=0.01, and -4.6+/-4.0%, P=0.1, respectiv ely, P=0.003 and P=0.005 compared with normal) as was an increase in medull ary perfusion (+58+/-21 in normal versus +24+/-11% in HC, P=0.04), A decrea se in the intratubular contrast media concentration in the distal tubule an d 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 renal excretory responses to SNP were similar between the groups. In c onclusion, early experimental HC in the pig attenuates renal perfusion resp onse to both endothelium-dependent and -independent vasodilators possibly b ecause of decreased bioavailability or decreased vascular responsiveness to nitric oxide. This vascular impairment may play a role in maladjusted reno vascular responses and contribute to renal damage in later stages of athero sclerosis.