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

• Published in: Acta pharmacologica Sinica Vol. 28; no. 10; pp. 1566 - 1572
• Main Authors: Anozie, Ogechukwu, Ross, Richonda, Oyekan, Adebayo O, Yakubu, Momoh A
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.10.2007
• Subjects: Animals; Antioxidants - pharmacology; Aorta - drug effects; Aorta - physiology; Ascorbic Acid - pharmacology; Bradykinin - pharmacology; Catalase - pharmacology; Endothelin-1 - pharmacology; In Vitro Techniques; Male; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Phenylephrine - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Superoxide Dismutase - pharmacology; Vasodilation - drug effects; Vasodilator Agents - pharmacology; 内皮缩血管肽-1; 抗氧化; 舒缓激肽; 苯肾上腺素; 过氧化物
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2007.00631.x

Aim： We tested the hypothesis that bradykinin （BK）-induced relaxation of phenylephrine （PE） and endothelin-1 （ET-1） contractions can be differentially modu- lated 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.