RENAL HEMODYNAMIC CONSEQUENCES OF HYPERLIPIDEMIA

Short-term dietary induced hypercholesterolemia in animals has been fo und to cause either increased vascular tone in various blood vessels, such as coronary arteries and renal vasculature, or impaired relaxatio n to endothelial-dependent vasodilators. In the kidney, renal blood fl ow, glomerular filtration rate and ultrafiltration coefficient are dec reased whereas glomerular capillary pressure is elevated. These findin gs indicate pre- and postglomerular constriction and mesangial cell co ntraction. Most evidence indicates that oxidized low density lipoprote in (ox-LDL) is responsible for initiating these functional abnormaliti es, and that it affects the endothelium rather than vascular smooth mu scle cells. Nitric oxide (NO) and prostaglandin production are increas ed, probably due to the effects of ox-LDL on endothelial cell membrane s. Vasoconstrictor prostaglandins and accelerated inactivation of NO b y reactive oxygen species appear to play important roles in the impair ed 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 mat rix synthesis.