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Vasodilatory action of trans ‐4‐methoxy‐β‐nitrostyrene in rat isolated pulmonary artery
Author(s) -
ArrudaBarbosa Loeste,
VasconcelosSilva Alfredo Augusto,
Borges Rosivaldo Santos,
Duarte Gloria Pinto,
Magalhães Pedro Jorge Caldas,
Lahlou Saad
Publication year - 2021
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 - 10.1111/1440-1681.13467
Subject(s) - phenylephrine , verapamil , vasodilation , tetraethylammonium , chemistry , pulmonary artery , pharmacology , endothelium , potassium channel , pulmonary hypertension , soluble guanylyl cyclase , medicine , calcium , potassium , anesthesia , nitric oxide , guanylate cyclase , blood pressure , organic chemistry
Trans ‐4‐methoxy‐β‐nitrostyrene (T4MN) induced more potent vasorelaxant effects in resistance arteries from hypertensive rats than its parent drug, β‐nitrostyrene 1‐nitro‐2‐phenylethene (NPe). To better understand the influence of insertion of the electron‐releasing methoxy group in the aromatic ring of NPe, we investigated vasorelaxant effects of T4MN in isolated pulmonary artery and compared them with those of NPe in view of the potential interest of T4MN in pulmonary arterial hypertension. T4MN and NPe both caused concentration‐dependent vasorelaxation in pulmonary artery rings pre‐contracted with either phenylephrine (1 µmol/L) or KCl (60 mmol/L), an effect unaffected by endothelium removal. In endothelium‐intact preparations pre‐contracted with phenylephrine, the vasorelaxant effect of T4MN was more potent than that of NPe. However, unlike NPe, this effect was significantly reduced following pretreatment with 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) (10 µmol/L, a guanylate cyclase inhibitor) or tetraethylammonium (5 mmol/L, a potassium channel blocker). T4MN abolished the CaCl 2 ‐induced contractions in pulmonary artery preparations stimulated with phenylephrine (PHE) under Ca 2+ ‐free conditions in the presence of verapamil, to preferentially activate receptor‐operated calcium channels. From these findings, we propose that T4MN evokes endothelium‐independent vasorelaxant effects in isolated rat pulmonary artery, partially by inhibiting Ca 2+ influx through L‐type Ca 2+ channels, as well as by activating soluble guanylate cyclase and potassium channels. The present results suggest the therapeutic potential of T4MN in treating pulmonary arterial hypertension.