title: Nitric oxide attenuates the release of endothelium-derived hyperpolarizing factor.
abstract: BACKGROUND
  The contribution of the endothelium-derived hyperpolarizing factor (EDHF), proposed to be a cytochrome P450-derived metabolite of arachidonic acid, to endothelium-dependent dilatation under physiological conditions has yet to be established, because its effect can be detected only after inhibition of NO synthase and cyclooxygenase. The possibility that NO exerts a feedback inhibition on EDHF formation was studied in isolated perfused arterial segments.
  
  
  RESULTS
  Under combined blockade of NO synthase and cyclooxygenase, the EDHF-mediated vasodilatation elicited by receptor-dependent agonists in rabbit carotid and porcine coronary arteries was significantly attenuated by the NO donors C87-3786 and CAS 1609. The endothelium-independent dilatation elicited by isoproterenol was not altered by either NO donor. In NG-nitro-L-arginine-treated carotid artery segments, C87-3786 significantly attenuated the acetylcholine-induced increase in 6-keto-prostaglandin F1 alpha release, which was taken as an index of arachidonic acid liberation. In parallel experiments using cultured human endothelial cells, C87-3786 attenuated the Ca2+ response to bradykinin. The release of EDHF from a luminally perfused porcine coronary artery was detected by recording the membrane potential of downstream-situated cultured rat aortic smooth muscle cells. The NO donor C87-3786 had no effect on the hyperpolarization elicited by preformed EDHF but markedly inhibited its release from bradykinin-stimulated donor segments.
  
  
  CONCLUSIONS
  These findings indicate that under physiological conditions, the production of EDHF is damped by NO. Therefore, it follows that when NO synthesis is impaired, alleviation of this intrinsic inhibition may, at least in part, maintain endothelial vasodilator function.
authors.affiliation: Zentrum der Physiologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Bauersachs
authors.forename: R
authors.initials: R
authors.lastname: Popp
authors.forename: M
authors.initials: M
authors.lastname: Hecker
authors.forename: E
authors.initials: E
authors.lastname: Sauer
authors.forename: I
authors.initials: I
authors.lastname: Fleming
authors.forename: R
authors.initials: R
authors.lastname: Busse
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001685:Biological Factors / Q000096:biosynthesis / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D015398:Signal Transduction; D013552:Swine; D014471:Umbilical Veins; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C094475:4-hydroxynethyl-furoxan-3-carboxamide; D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D009603:Nitroso Compounds; D010069:Oxadiazoles; D010880:Piperidines; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; C080068:C 873786; D019335:Nitroarginine; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D001920:Bradykinin; D002118:Calcium