Journal of the American Society of Nephrology : JASN
-
J. Am. Soc. Nephrol. · Apr 2004
Hypercholesterolemia in rats induces podocyte stress and decreases renal cortical nitric oxide synthesis via an angiotensin II type 1 receptor-sensitive mechanism.
Podocyte stress precedes proteinuria in hypercholesterolemic rats. Molsidomine, a nitric oxide (NO) donor, prevented podocyte stress and proteinuria in long-term hypercholesterolemia, suggesting that podocyte stress was due to NO deficiency. Podocytes express the angiotensin II type 1 receptor, which influences their function. ⋯ Finally, hypercholesterolemia decreased renal cortical NO synthase activity and increased caveolin-1 protein mass and glomerular caveolin staining, and these changes were also prevented by losartan. It is suggested that podocyte stress in these models of early injury results from angiotensin II, unopposed by the action of endogenous NO. This underscores the strategic role of angiotensin II blockers in early kidney disease.