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Mechanisms underlying the vasorelaxant effect of trans‐4‐methoxy‐&bgr;‐nitrostyrene in the rat mesenteric resistance arteries

Thayane Rebeca Alves-Santos,F. E. Xavier,G. P. Duarte,Rosivaldo dos Santos Borges,P. Magalhães,S. Lahlou

Published 2019 in European Journal of Pharmacology

ABSTRACT

ABSTRACT Mechanisms underlying the vasorelaxant effects of the synthetic nitro compound, trans‐4‐methoxy‐&bgr;‐nitrostyrene (T4MN) were studied in isolated small resistance arteries from spontaneously hypertensive rats (SHRs). T4MN caused vasorelaxation in endothelium‐intact third‐order branches of the mesenteric artery pre‐contracted with noradrenaline (NA). This effect was unchanged by indomethacin and atropine but was significantly reduced by endothelium removal, L‐NAME, LY294002, glybenclamide, TEA, apamin, TRAM 34, or by the association of apamin and TRAM 34. Pretreatment with the sGC inhibitor, 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) reduced the T4MN‐induced relaxation in endothelium‐intact, but not in denuded preparations. Incubation of small resistance arteries with T4MN increased nitric oxide (NO) production, an effect that was blocked by L‐NAME. In Ca2+‐free medium, T4MN inhibits the contractions induced by (i) NA, (ii) exogenous calcium through receptor‐ or voltage‐operated Ca2+ channels and (iii) those evoked by Ca2+ influx through stores‐operated Ca2+ channels activated by thapsigargin‐induced Ca2+ store depletion. In contrast, T4MN was inert against the transient contraction induced by caffeine in Ca2+‐free medium. In conclusion, T4MN induced effective vasorelaxant effects in isolated small resistance arteries from SHRs. This vasorelaxation seems to be mediated partly by an endothelium‐dependent mechanism involving activation of Akt/eNOS/NO pathway and partly by an endothelium‐independent mechanism through activation of sGC/cGMP/PKG pathway in vascular smooth muscle, leading to inhibition of Ca2+ influx from the extracellular milieu and IP3‐sensitive intracellular Ca2+ release as well as activation of potassium channels. Graphical abstract Figure. No Caption available.

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