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Terminalia avicennioides causes redox-sensitive endothelium-dependent relaxation involving nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing in porcine coronary artery and different conductance and resistance vessels from rats

Mbaye Sene, Hyunho Lee, Ibrahima Diouf, Maimouna Toure, Catherine Vonthron Senecheau, Cyril Auger, Mamadou Sarr, Valerie Schini Kerth, Modou Oumy Kane.




Abstract
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Background: Our work is part of the enhancement of plants of Senegalese pharmacopeia with cardiovascular aim, among which Terminalia avicennioides.

Aim and Objective: The aim of this study was to determine whether a hydroethanolic bark extract of T. avicennioides (TAE) is able to induce a relaxant effect in porcine coronary, rat mesenteric artery, carotid, femoral arteries, and thoracic aorta and to determine the mechanism underlying this effect.

Materials and Methods: Porcine coronary, rat mesenteric, carotid, femoral arteries, and thoracic aorta rings were suspended in organ chambers for the recording of changes in isometric forces. Rings with endothelium were incubated or not with L-Nitro Arginine to block nitric oxide (NO) synthase, MnTMPyP, polyethylene glycol catalase (CAT), an inhibitors of intracellular production reactive oxygen species; CAT, an inhibitor of extracellular reactive oxygen species; Wortmannin, an inhibitor of redox-sensitive pathway PI3 kinase/Akt; PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d]pyrimidine), an inhibitor of Src kinase; apamin (APA) an inhibitor of small conductance potassium channels calcium-dependent (SKCa) and Tram-34 an inhibitor of intermediary conductance potassium channels calcium-dependent (IKCa); and indomethacin (INDO), an inhibitor of cyclooxygenase before contraction with U46619 or phenylephrine (PE) and a concentration relaxation curve to TAE. In some experiments, the endothelium was removed before contraction with U46619 or PE and concentration relaxation to TAE. The phosphorylation level of Akt and eNOS was assessed by Western blot analysis.

Results: The hydroethanolic bark TAE induces a vasodilatory effect in porcine coronary artery precontracted with U46619. This effect is endothelium-dependent and is mediated by NO, prostaglandin, and endothelium-derived hyperpolarizing. TAE also induces vasorelaxant effects in superior mesenteric arteries, carotid arteries, thoracic aorta, and femoral arteries from rat.

Conclusion: TAE-induced sustaining phosphorylation of Akt and eNOS in endothelial cells. T. avicennioides induces vascular relaxation which can explain the benefic effect of this plant in the treatment of high blood pressure in Senegal.

Key words: Terminalia avicennioides; Vasorelaxant Effects; Porcine Coronary; Rat Artery






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