title: Differential modulation of bradykinin-induced relaxation of endothelin-1 and phenylephrine contractions of rat aorta by antioxidants.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Vascular Biology Unit, Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas 77004, USA.
authors: Ogechukwu
authors: O
authors: Anozie
authors: Richonda
authors: R
authors: Ross
authors: Adebayo O
authors: AO
authors: Oyekan
authors: Momoh A
authors: MA
authors: Yakubu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001205:Ascorbic Acid / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D019332:Endothelin-1; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D010656:Phenylephrine; D002374:Catalase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; D001920:Bradykinin