In vivo renal vascular and tubular function in experimental hypercholesterolemia

Area of Science:

• Nephrology
• Cardiovascular Physiology
• Experimental Medicine

Background:

• Hypercholesterolemia (HC) is linked to impaired vascular responses, likely due to reduced nitric oxide bioavailability.
• Understanding HC's impact on renal function is crucial for managing associated cardiovascular risks.

Purpose of the Study:

• To investigate the effects of experimental hypercholesterolemia on renal vascular and tubular function in pigs.
• To assess the impact of HC on nitric oxide-mediated and independent renal vasodilation.

Main Methods:

• Domestic pigs were fed either a normal or a high-cholesterol diet for 12 weeks.
• Renal perfusion and intratubular contrast media concentration were measured using electron-beam computed tomography.
• Vascular and tubular responses were evaluated following infusions of acetylcholine and sodium nitroprusside.

Main Results:

• Hypercholesterolemia blunted the increase in cortical and medullary perfusion in response to acetylcholine and sodium nitroprusside.
• Renal tubular fluid reabsorption and sodium excretion were altered in hypercholesterolemic pigs.
• While responses to sodium nitroprusside were similar, acetylcholine-induced changes were significantly reduced in the HC group.

Conclusions:

• Early experimental hypercholesterolemia attenuates renal perfusion responses to both endothelium-dependent and -independent vasodilators.
• This impairment may stem from decreased nitric oxide bioavailability or vascular responsiveness.
• The observed vascular dysfunction could contribute to maladjusted renovascular responses and kidney damage in atherosclerosis.