CEREBROARTERIAL RELAXATIONS MEDIATED BY NITRIC-OXIDE DERIVED FROM ENDOTHELIUM AND VASODILATOR NERVE

Purposes of this study were to determine whether: (1) nitric oxide is involved in endothelium-dependent relaxation in helical strips of dog cerebral arteries; (2) relaxing factor distinct from NO is also involv ed, and (3) susceptibility to N(G)-nitro-L-arginine (L-NA), an NO synt hase inhibitor, of the response to mediators liberating NO from the en dothelium and nerve differs. Changes in isometric tension were recorde d. In the strips contracted with prostaglandin F2alpha, substance P an d arginine vasopressin produced a relaxation which was abolished or re versed to a contraction by endothelium denudation. The relaxations wer e not influenced by indomethacin but were suppressed dose-dependently by L-NA, as was the response to nicotine that stimulates the non-adren ergic, non-cholinergic vasodilator nerve and liberates NO. The inhibit ions were reversed by L- but not D-arginine. NO (acidified NaNO2)-indu ced relaxations were not reduced by L-NA. The inhibitory effect was gr eater in the responses to vasopressin than substance P; however, there was no significant difference in the response to nicotine vs. the pep tides. Substance P increased the level of cyclic guanosine monophospha te (GMP) in the artery strips with the intact endothelium, the effect being abolished by endothelium denudation, L-NA and oxyhemoglobin. Rel axations caused by adenosine triphosphate (ATP) and adenosine diphosph ate (ADP) were dependent partially on the endothelium. Treatment with L-NA attenuated the ATP-induced relaxation in the strips with endothel ium but did not alter the response of denuded strips. It may be conclu ded that endothelium-dependent relaxations caused by substance P, vaso pressin, ATP and ADP in dog cerebral arteries are mediated solely via NO that activates guanylate cyclase and increases the production of cy clic GMP. Susceptibility to L-NA of NO synthase in the endothelium and vasodilator nerve does not appear to differ significantly.