Differential modulation of bradykinin-induced relaxation of endothelin-1 and phenylephrine contractions of rat aorta by antioxidants
AbstractAim: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 (1×10−9−1×10−5 mol/L)- and ET-1 (1×10−10−1×10−8 mol/L)-induced contractions and the influence of ROS in BK (1×10−9−1×10−5 mol/L) relaxation of PE (1×10−7 mol/L) or ET-1 (1×10−9 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 (1×10−4 mol/L).Results:Tension generated by ET-1 (1 ×10−9 mol/L) or PE (1×10−7 mol/L) was differentially relaxed by BK (1×10−5 mol/L), producing a maximal relaxation of 75%±5% and 35±4%, respectively. The BK (1×10−5 mol/L)-induced relaxation of PE (1×10−7 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 (1×10−9 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 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.