Vasorelaxant effects of 2-nitro-1-phenyl-1-propanol in rat aorta
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 contraction...
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Published in | Clinical and experimental pharmacology & physiology Vol. 43; no. 11; pp. 1054 - 1061 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Australia
Blackwell Publishing Ltd
01.11.2016
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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 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. |
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Bibliography: | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) istex:DB8D2BAAA399805F99D6B1F3646BA9A42F9EFB2C ark:/67375/WNG-QMNSGFDB-V ArticleID:CEP12625 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0305-1870 1440-1681 |
DOI: | 10.1111/1440-1681.12625 |