Role of nitric oxide in angiotensin IV-induced increases in cerebral blood flow

The present study investigated the effects of three newly synthesized AngIV analogs (Lysine1-AngIV, Norleucine1-AngIV, and Norleucinal) on cerebral blood flow (CBF) in anesthetized Sprague-Dawley rats utilizing laser-Doppler flowmetry. The results indicate that internal carotid infusions of AngIV, Norleucine1-AngIV, Norleucinal, and Lysine1-AngIV increased CBF above baseline by 25, 32, 33 and 44%, respectively, without changing systemic arterial blood pressure. In a second experiment separate groups of rats were pretreated with nitric oxide (NO) synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) or saline, followed by AngIV or Norleucinal for the purpose of evaluating the hypothesis that the mechanism of action of these compounds is linked to the release of NO. Pretreatment with saline followed by AngIV and Norleucinal increased CBF by 29 and 39%, respectively, while pretreatment with L-NAME blocked the vasodilatory effects of AngIV and Norleucinal, suggesting that the increment in blood flow induced by these compounds is dependent upon the synthesis and release of NO from vascular endothelial cells.