Renal vascular function in hypercholesterolemia is preserved by chronic antioxidant supplementation

Hypercholesterolemia impairs systemic vascular reactivity in response to en dothelium-dependent vasodilators. which may be mediated partly through incr eased formation of lipid peroxides. However, it is unclear whether these pa thophysiological mechanisms play a role in renal vascular impairment in exp erimental hypercholesterolemia. Hence. pigs were studied after a 3-mo norma l (n=7) or high cholesterol (HC) (n=7) diet, HC diet supplemented daily wit h antioxidant vitamins E (100 IU/kg) and C (1000 mg, HC+vitamins, n=5), or normal diet supplemented with vitamins,(N+ vitamins, n=5). Renal blood flow was measured with electron-beam computed tomography before and during infu sion of acetylcholine (Ach). Endothelial function, endothelial and inducibl e nitric oxide synthase (NOS), and nitrotyrosine immunoreactivity were stud ied in renal arteries ex vivo. Despite similar cholesterol levels. LDL oxid izability (lag time, malondialdehyde, and relative electrophoretic mobility ) was increased in pigs that were fed the HC diet but was significantly dec reased in pigs that were fed the HC+vitamins diet. Renal blood now response to Ach was blunted in pigs that were fed the HC diet but was preserved in pigs that were fed the HC+vitamins diet. Maximal relaxation to Ach was atte nuated in pigs that were fed the HC diet compared with those that were fed the normal diet (51.5 +/-6.4% versus 97.0 +/-2.9%; P<0.01) but was preserve d in pigs that were fed the HC+vitamins diet (103.1<plus/minus>3.0%: P=0.39 ) and N+ vitamins diet (87.7 +/-3.0%; P=0.1), as were relaxation responses to calcium ionophore A23187. Vascular smooth-muscle relaxation to diethylam ine was enhanced in endothelium-denuded HC vessel but was restored in pigs that were on the HC+vitamins regimen. In HC, immunoreactivity of endothelia l NOS was decreased, that of inducible NOS was increased, and both were pre served in pigs that were fed the HC+vitamins and N+vitamins diets. whereas nitrotyrosine was not detected. The present study demonstrates that antioxi dant intervention in experimental HC reduces LDL oxidizability and preserve s renal vascular responses to endothelium-dependent vasodilators. Therefore , this beneficial effect potentially can protect the kidney from hyperchole sterolemia-induced damage.