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 (Lysine(1)-AngIV Norleucine(1)-AngIV, and Norleucinal) o n cerebral blood flow (CBF) in anesthetized Sprague-Dawley rats utiliz ing laser Doppler flowmetry. The results indicate that internal caroti d infusions of AngIV, Norleucine(1)-AngIV, Norleucinal, and Lysine(1)- AngIV increased CBF above baseline by 25, 32, 33 and 44%, respectively , without changing systemic arterial blood pressure. In a second exper iment separate groups of rats were pretreated with nitric oxide (NO) s ynthase inhibitor, N-w-nitro-L arginine methyl ester (L-NAME) or salin e, followed by AngIV or Norleucinal for the purpose of evaluating the hypothesis that the mechanism of action of these compounds is linked t o the release of NO. Pretreatment with saline followed by AngIV and No rleucinal increased CBF by 29 and 39%, respectively, while pretreatmen t with L-NAME blocked the vasodilatory effects of AngIV and Norleucina l, suggesting that the increment in blood flow induced by these compou nds is dependent upon the synthesis and release of NO from vascular en dothelial cells. (C) 1998 Published by Elsevier Science BN.