Mechanism of the vasorelaxant effect induced by trans-4-methyl-[beta]-nitrostyrene, a synthetic nitroderivative, in rat thoracic aorta

• Published in: Clinical and experimental pharmacology & physiology Vol. 44; no. 7; p. 787
• Main Authors: Teofilo, Taylena Maria, Arruda-Barbosa, Loeste, Rodrigues-Silva, Jussara Mathyelle, Vale, Joyce Karen Lima, Borges, Rosivaldo Santos, Duarte, Gloria Pinto, Magalhaes, Pedro Jorge Caldas, Lahlou, Saad
• Format: Journal Article
• Language: English
• Published: Richmond Wiley Subscription Services, Inc 01-07-2017
• Subjects: Aorta; Caffeine; Calcium (extracellular); Calcium (intracellular); Calcium chloride; Calcium influx; Calcium ions; Depletion; Endothelium; Indomethacin; NG-Nitroarginine methyl ester; Phenylephrine; Phosphorylation; Potassium chloride; Pretreatment; Protein kinase C; Protein-tyrosine-phosphatase; Restoration; Rodents; Sodium; Sodium orthovanadate; Tetraethylammonium; Thapsigargin; Thorax; Tyrosine; Vasodilation; Verapamil
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12771

Summary Mechanisms underlying the vasorelaxant effects of trans-4-methyl-[beta]-nitrostyrene (T4MeN) were studied in rat aortic rings. In endothelium-intact preparations, T4MeN fully and similarly relaxed contractions induced by phenylephrine (PHE) (IC50 = 61.41 [35.40-87.42] µmol/L) and KCl (IC50 = 83.50 [56.63-110.50] µmol/L). The vasorelaxant effect of T4MeN was unchanged by endothelium removal, pretreatment with L-NAME, indomethacin, tetraethylammonium, ODQ or MDL-12,330A. Under Ca2+-free conditions, T4MeN significantly reduced with a similar potency: (i) phasic contractions induced by PHE, but not by caffeine; (ii) contractions due to CaCl2 in aortic preparations stimulated with PHE (in the presence of verapamil) or high KCl; (iii) contractions evoked by the restoration of external Ca2+ levels after depletion of intracellular Ca2+ stores in the presence of thapsigargin. In contrast, T4MeN was more potent at inhibiting contractions evoked by the tyrosine phosphatase inhibitor, sodium orthovanadate, than those induced by the activator of PKC, phorbol-12,13-dibutyrate. These results suggest that T4MeN induces an endothelium- independent vasorelaxation that appears to occur intracellularly through the inhibition of contractions that are independent of Ca2+ influx from the extracellular milieu but involve phosphorylation of tyrosine residues.