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.