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

We tested the hypothesis that bradykinin (BK)-induced relaxation of phenylephrine (PE) and endothelin-1 (ET-1) contractions can be differentially modulated by reactive oxygen species (ROS).

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.

Aortic rings isolated from Sprague-Dawley rats were used for the study. The contribution of ROS to PE (1 x 10(-9)-1 x 10(-5) mol/L)- and ET-1 (1 x 10(-10)-1 x 10(-8) mol/L)-induced contractions and the influence of ROS in BK (1 x 10(-9)-1 x 10(-5) mol/L) relaxation of PE (1 x 10(-7) mol/L) or ET-1 (1 x 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 x 10(-4) mol/L).

Tension generated by ET-1 (1 x 10(-9) mol/L) or PE (1 x 10(-7) mol/L) was differentially relaxed by BK (1 x 10(-5) mol/L), producing a maximal relaxation of 75%+/-5% and 35+/-4%, respectively. The BK (1 x 10(-5) mol/L)-induced relaxation of PE (1 x 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 x 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.