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

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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 (1×10−9−1×10−5mol/L)- and ET-1 (1×10−10−1×10−8mol/L)-induced contractions and the influence of ROS in BK (1×10−9−1×10−5mol/L) relaxation of PE (1×10−7mol/L) or ET-1 (1×10−9mol/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 (1×10−4mol/L). Results: Tension generated by ET-1 (1 ×1 0−9mol/L) or PE (1×10−7mol/L) was differentially relaxed by BK (1×10−5mol/L), producing a maximal relaxation of 75%±5% and 35±4%, respectively. The BK (1×10−5mol/L)-induced relaxation of PE (1×10−7mol/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 (1×10−9mol/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 O2and H2 O2 differentially modulate BK relaxation in an agonist-specific manner. O2attenuates BK-induced relaxation of PE contraction, but contributes to the relaxation of ET-1 contraction. O2seems to inhibit PE contraction, while H2 O2 contributes to ET-1-induced contraction. Thus, ROS differentially modulate vascular tone depending on the vasoactive agent that is used to generate the tone.

Keywords: anti-oxidants; bradykinin; contraction; endothelin-1; hydrogen peroxide; phenylephrine; reactive oxygen species; relaxation; superoxide

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2007.00631.x

Affiliations: Vascular Biology Unit, Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas 77004, USA

Publication date: October 1, 2007

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