Role of NO in endothelium-dependent relaxation of rabbit basilar artery in situ.
The purpose of this study was to investigate the possible involvement of endothelium-derived hyperpolarizing factor in endothelium-dependent relaxation of the cerebral vasculature by testing the effectiveness of NO synthase inhibitors at inhibiting endothelium-dependent relaxation in the rabbit basilar artery. Acetylcholine (1.0 microM) and 0.1/0.2 microM sarafotoxin S6c, an endothelinB receptor agonist, relaxed serotonin constricted basilar artery in situ by 100% and 70%, respectively. NG-monomethyl-L-arginine (L-NMMA; 0.1 mM) and 0.3 mM NG-nitro-L-arginine (L-NNA), NO synthase inhibitors, decreased the 1.0 microM acetylcholine- and 0.1/0.2 microM sarafotoxin S6c-induced relaxations by 75% and 45%, respectively. Unexpectedly, the relaxations were abolished by the combination of L-NMMA plus L-NNA. Furthermore, L-arginine (1.0 mM), but not D-arginine, restored the relaxations. Sodium nitroprusside-induced relaxation was also inhibited by L-NMMA plus L-NNA, and the inhibition was reversed by L-arginine. KCl constricted vessels only minimally relaxed in response to sodium nitroprusside, acetylcholine, and sarafotoxin S6c. These results demonstrate that combined NO synthase inhibitors more effectively inhibit endothelium-dependent relaxation than a single inhibitor. The mechanism underlying the greater inhibition due to the combined NO synthase inhibitors may result from both decreased NO release and secondary effects caused by decreased NO release, such as membrane depolarization. The results further suggest that caution should be used with respect to suggestions of the involvement of endothelium-derived hyperpolarizing factor in endothelium-dependent relaxation based upon the partial inhibitory effects of NO synthase inhibitors.
Zuccarello
M
M
Department of Neurosurgery, University of Cincinnati College of Medicine, OH 45267-0575, USA.
Boccaletti
R
R
Rapoport
R M
RM
D000818:Animals; D001488:Basilar Artery / Q000502:physiology*; D004338:Drug Combinations; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase