Effect of an endothelin receptor antagonist Bosentan in spontaneously hypertensive rats (SHR) and control Wistar –Kyoto (WKY) rats

Written by Antal Mónika, Brassai Attila

Introduction: ET-1 is a potent vasoconstrictor peptide involved in the regulation of vascular tone, exerts vasoactive, pro-inflammatory, hypertrophic, and profibrotic properties on the heart, kidney, and blood vessels. To attenuate this effects endothelin receptor antagonists (ERA) are improved in this process, mainly the treatement with bosentan.Objective: The effect of the combined ET-A/ET-B endothelin receptor antagonist bosentan was evaluated in spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats, to determine the contarctil characteristics of ET-1, to evaluate the vascular changes due to bosentan treatement. Methods: The rats were anesthetized before the midline incision, by isolation of mesenteric artery we prepared small rings which were introduced in Krebs solution. The vascular changes were examined also with intact endotelium and with endotelium-denuded mesenteric vessels, in the presence of increasing concentrations of ET-1.To investigate the contribution of ERA in SHR and control WKY vascular relaxation we examined the two separated groups by adding cumulated doses of bosentan. Results: In the presence of ET-1 the contractil responses was significantly higher in WKY than SHR, but the bosentan relaxation indicated a quite similar response in both mesenteric vessels.Conclusion: These results suggest that there are interactions among the two tipes of vessels, there was no significant difference between the relaxation responses, which represents an approximative effect of bosentan in alteration of the blood pressure in SHR.

 

Keywords: Bosentan, hypertensive rats, mesenteric artery, contractility, relaxation response


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