Renal hemodynamic consequences of hyperlipidemia.

Abstract

Short-term dietary induced hypercholesterolemia in animals has been found to cause either increased vascular tone in various blood vessels, such as coronary arteries and renal vasculature, or impaired relaxation to endothelial-dependent vasodilators. In the kidney, renal blood flow, glomerular filtration rate and ultrafiltration coefficient are decreased whereas glomerular capillary pressure is elevated. These findings indicate pre- and post-glomerular constriction and mesangial cell contraction. Most evidence indicates that oxidized low density lipoprotein (ox-LDL) is responsible for initiating these functional abnormalities, and that it affects the endothelium rather than vascular smooth muscle cells. Nitric oxide (NO) and prostaglandin production are increased, probably due to the effects of ox-LDL on endothelial cell membranes. Vasoconstrictor prostaglandins and accelerated inactivation of NO by reactive oxygen species appear to play important roles in the impaired relaxation response. These endothelial abnormalities are postulated to contribute to progressive glomerulosclerosis via local hemodynamic changes and/or direct effects on mesangial cell proliferation and matrix synthesis.