Effect of NO on EDHF response in rat middle cerebral arteries.
Whereas the actual identity of endothelium-derived hyperpolarizing factor (EDHF) is still not certain, it involves a process requiring the endothelium and eliciting hyperpolarization and relaxation of smooth muscle. It is neither nitric oxide (NO) nor prostacyclin, and its presence has been demonstrated in a variety of vessels. Recent studies in peripheral vessels report that EDHF-mediated dilations were either attenuated or blocked by NO. Studies presented here demonstrate that NO does not block EDHF-mediated dilations in cerebral vessels. Rat middle cerebral arteries were cannulated, pressurized, and luminally perfused. EDHF-mediated dilations were elicited by the luminal application of ATP in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin (inhibitors of NO synthase and cyclooxygenase, respectively). These dilations persisted when S-nitroso-N-acetylpenicillamine, an NO donor, was added exogenously in the presence of L-NAME, or when endogenous NO was present but its cGMP actions were blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of guanylate cyclase. These findings demonstrate that the EDHF response is not suppressed by NO in cerebral vessels and suggests a role for EDHF during normal physiological conditions.
Schildmeyer
Lisa A
LA
Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Bryan
Robert M
RM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013873:Thionucleotides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; C110881:S-nitro-N-acetylpenicillamine; D013873:Thionucleotides; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D010396:Penicillamine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; C008501:2-methylthio-ATP