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Vasorelaxant effects of 2‐nitro‐1‐phenyl‐1‐propanol in rat aorta
Author(s) -
Brito Teresinha Silva,
BatistaLima Francisco José,
Gadelha Kalinne Kelly Lima,
FonsecaMagalhães Patrícia Andrea,
Lahlou Saad,
Magalhães Pedro Jorge Caldas
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12625
Subject(s) - phenylephrine , chemistry , tetraethylammonium , glibenclamide , vasodilation , medicine , endocrinology , adenosine , adenylyl cyclase , soluble guanylyl cyclase , pharmacology , nitric oxide , biochemistry , potassium , enzyme , organic chemistry , guanylate cyclase , blood pressure , diabetes mellitus
Summary 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 1 H ‐[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 Ca 2+ 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 Ca 2+ 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 Ca 2+ ‐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.