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Differential modulation of bradykinin-induced relaxation of endothelin-1 and phenylephrine contractions of rat aorta by antioxidants

  
@article{APS5866,
	author = {Ogechukwu Anozie and Richonda Ross and Adebayo O Oyekan and Momoh A Yakubu},
	title = {Differential modulation of bradykinin-induced relaxation of endothelin-1 and phenylephrine contractions of rat aorta by antioxidants},
	journal = {Acta Pharmacologica Sinica},
	volume = {28},
	number = {10},
	year = {2016},
	keywords = {},
	abstract = {Aim: We tested the hypothesis that bradykinin (BK)-induced relaxation of phe-nylephrine (PE) and endothelin-1 (ET-1) contractions can be differentially modulated by reactive oxygen species (ROS).
Methods: Aortic rings isolated from Sprague-Dawley rats were used for the study. The contribution of ROS to PE (1times10-9-1times10-5 mol/L)- and ET-1 (1times10-10-1times10-8 mol/L)-induced contractions and the influence of ROS in BK (1times10-9-1times10-5 mol/L) relaxation of PE (1times10-7 mol/L) or ET-1 (1times10-9 mol/L)-induced tension was evaluated in the aorta in the presence or absence of the following antioxidants: catalase (CAT, 300 U/mL), superoxide dismutase (SOD, 300 U/mL), and vitamin C (1times10-4 mol/L).
Results: Tension generated by ET-1 (1 times10-9 mol/L) or PE (1times10-7 mol/L) was differentially relaxed by BK (1times10-5 mol/L), producing a maximal relaxation of 75%plusminus5% and 35plusminus4%, respectively. The BK (1times10-5 mol/L)-induced relaxation of PE (1times10-7 mol/L) tension was significantly enhanced from 35%plusminus4% (control) to 56%plusminus9%, 60%plusminus5%, and 49%plusminus6% by SOD, CAT, and vitamin C, respectively (P < 0.05, n =8). However, the relaxation of ET-1 (1times10-9 mol/L) tension was significantly attenuated from 75%plusminus5% (control) to 37%plusminus9%, 63%plusminus4%, and 39%plusminus7% by SOD, CAT, and vitamin C, respectively (P < 0.05, n =8). On the other hand, CAT had no effect on PE-induced tension, while SOD enhanced PE-induced tension (36%, P < 0.05, n =10) and vitamin C attenuated (66%, P < 0.05, n = 8) the tension induced by PE. By contrast, SOD or vitamin C had no effect, but CAT attenuated (44%, P < 0.05, n = 9) the tension induced by ET-1.
Conclusion: We have demonstrated that O2- and H2O2 differentially modulate BK relaxation in an agonist-specific manner. O2- attenuates BK-induced relaxation of PE contraction, but contributes to the relaxation of ET-1 contraction. O2- seems to inhibit PE contraction, while H2O2 contributes to ET-1-induced contraction. Thus, ROS differentially modulate vascular tone depending on the vasoactive agent that is used to generate the tone.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/5866}
}