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

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 (1x10(-9)-1x10(-5)mol/L)- and ET-1 (1x10(-10)-1x10(-8)mol/L)-induced contractions and the influence of ROS in BK (1x10(-9)-1x10(-5)mol/L) relaxation of PE (1x10(-7)mol/L) or ET-1 (1x10(-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 (1x10(-4)mol/L). Results: Tension generated by ET-1 (1 x1 0(-9)mol/L) or PE (1x10(-7)mol/L) was differentially relaxed by BK (1x10(-5)mol/L), producing a maximal relaxation of 75%+/- 5% and 35 +/- 4%, respectively. The BK (1x10(-5)mol/L)-induced relaxation of PE (1x10(-7)mol/L) tension was significantly enhanced from 35%+/- 4% (control) to 56%+/- 9%, 60%+/- 5%, and 49%+/- 6% by SOD, CAT, and vitamin C, respectively (P < 0.05, n =8). However, the relaxation of ET-1 (1x10(-9)mol/L) tension was significantly attenuated from 75%+/- 5% (control) to 37%+/- 9%, 63%+/- 4%, and 39%+/- 7% 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 C AT attenuated (44%, P < 0.05, n =9) the tension induced by ET-1. Conclusion: We have demonstrated that O(2)(-)and H-2 O-2 differentially modulate BK relaxation in an agonist-specific manner. O(2)(-)attenuates BK-induced relaxation of PE contraction, but contributes to the relaxation of ET-1 contraction. O(2)(-)seems to inhibit PE contraction, while H-2 O-2 contributes to ET-1-induced contraction. Thus, ROS differentially modulate vascular tone depending on the vasoactive agent that is used to generate the tone.