Vasodilatory action of trans-4-methoxy-β-nitrostyrene in rat isolated pulmonary artery
| Autor: | Loeste Arruda-Barbosa, Rosivaldo S. Borges, Gloria Pinto Duarte, Alfredo Augusto Vasconcelos-Silva, Saad Lahlou, Pedro Jorge Caldas Magalhães |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Vasodilation Pharmacology Pulmonary Artery Styrenes 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) medicine.artery medicine Animals Phenylephrine Tetraethylammonium Voltage-dependent calcium channel Potassium channel blocker Potassium channel Rats 030104 developmental biology chemistry 030220 oncology & carcinogenesis Pulmonary artery Verapamil medicine.drug |
| Zdroj: | Clinical and experimental pharmacologyphysiologyREFERENCES. 48(5) |
| ISSN: | 1440-1681 |
| Popis: | 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 CaCl2 -induced contractions in pulmonary artery preparations stimulated with phenylephrine (PHE) under Ca2+ -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 Ca2+ influx through L-type Ca2+ 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. |
| Databáze: | OpenAIRE |
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