title: Vasorelaxant effects of 2-nitro-1-phenyl-1-propanol in rat aorta.
abstract: 2-Nitro-1-phenyl-1-propanol (NPP) is a nitro alcohol that is known as an intermediate in the synthesis of sympathomimetic agents, such as norephedrine. The present study investigated the vasoactive effects of NPP on rat aorta. In endothelium-intact aortic rings, NPP fully relaxed contractions that were induced by phenylephrine, KCl, and U-46619. The relaxant effects of NPP on phenylephrine-elicited contractions remained unaffected by NG-nitro-l-arginine methyl ester (l-NAME), indomethacin, propranolol, tetraethylammonium, 4-aminopyridine, and glibenclamide. Conversely, pretreatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL-12,330A), and N-[2-(P-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89) reduced the ability of NPP to relax contractions that were elicited by phenylephrine. NPP inhibited the vasoconstrictor response that was induced by Ca2+in aortic rings that were stimulated by pharmacomechanical or electromechanical coupling with phenylephrine and 60 mmol/L KCl, respectively, and after the depletion of intracellular Ca2+stores. Such effects of NPP were significantly reversed by pretreatment with the guanylyl cyclase inhibitor ODQ and weakly influenced by the adenylyl cyclase inhibitor MDL-12,330A. In Ca2+-free medium, NPP inhibited transient contractions that were induced by phenylephrine but not caffeine. In homogenates of aortic rings, NPP increased cyclic guanosine 3',5'-monophosphate (cGMP) and cyclic adenosine 3'-5'-monophosphate levels, but this effect was statistically significant only for cGMP. In conclusion, in contrast to the vasoconstrictor amine norephedrine, NPP is a vasodilator in rat aorta, and its relaxant effects are likely attributable to cGMP production.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Teresinha Silva
authors.initials: TS
authors.lastname: de Brito
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Batista-Lima
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Kalinne Kelly Lima
authors.initials: KK
authors.lastname: Gadelha
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Patrícia Andrea
authors.initials: PA
authors.lastname: da Fonseca-Magalhães
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Saad
authors.initials: S
authors.lastname: Lahlou
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil. pjcmagal@ufc.br.
authors.forename: Pedro Jorge Caldas
authors.initials: PJ
authors.lastname: Magalhães
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009574:Nitro Compounds / Q000494:pharmacology*; D009924:Organ Culture Techniques; D020005:Propanols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C496417:2-nitropropanol; D009574:Nitro Compounds; D020005:Propanols; D014665:Vasodilator Agents
keywords: cyclic nucleotides; nitro compounds; norephedrine; vascular smooth muscle