TY - JOUR
T1 - In vivo renal vascular and tubular function in experimental hypercholesterolemia
AU - Feldstein, Ariel
AU - Krier, James D.
AU - Sarafov, Mint Hershman
AU - Lerman, Amir
AU - Best, Patricia J.M.
AU - Wilson, Stephanie H.
AU - Lerman, Lilach O.
PY - 1999/10
Y1 - 1999/10
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Blood flow
KW - Hypercholesterolemia
KW - Kidney
KW - Renal function
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U2 - 10.1161/01.hyp.34.4.859
DO - 10.1161/01.hyp.34.4.859
M3 - Article
C2 - 10523374
AN - SCOPUS:0032754043
SN - 0194-911X
VL - 34
SP - 859
EP - 864
JO - Hypertension
JF - Hypertension
IS - 4 II
ER -