Impaired Nitric Oxide Function in the Basilar Artery of the Obese Zucker Rat

Abstract

The effect of insulin-resistance syndrome on vascular function has been examined in isolated basilar arteries using the obese Zucker rat (OZR) and age-matched lean littermate controls (lean Zucker rat; LZR) at 36 weeks of age. The OZR showed significantly reduced oral glucose tolerance and increased body weight, blood pressure, proteinuria, plasma levels of triglycerides, cholesterol, and insulin compared with the LZR. The contractile response to serotonin was significantly increased in the OZR. Furthermore, contractions to serotonin in LZR but not OZR were enhanced in the presence of the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (NAME). Relaxations to acetylcholine (ACh), histamine, and A23187 were significantly reduced in precontracted arteries from the OZR. In the presence of NAME, histamine responses were significantly reduced whereas ACh and A23187 responses were almost abolished. Relaxations to free-radical nitric oxide (NO) and papaverine were not different in arteries from the OZR, even though responses to sodium nitroprusside were reduced in the OZR. Western blot and immunofluorescent quantitative analyses of eNOS content in cerebral microvessel fractions and basilar artery preparations, respectively, were not significantly different between OZR and LZR. The results suggest impairment in endothelial function resulting in reduced NO function in the basilar artery from the OZR.