Differential modulation of bradykinin-induced relaxation of endothelin-1 and phenylephrine contracti

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:wenhonghe
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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 modu-lated by reactive oxygen species (ROS).Methods:Aortic rings isolated fromSprague-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 andthe influence of ROS in BK (1×10~(-9)-1×10~(-5)mol/L) relaxation of PE (1×10~(-7) mol/L) orET-1 (1×10~(-9)mol/L)-induced tension was evaluated in the aorta in the presence orabsence of the following antioxidants:catalase (CAT,300 U/mL),superoxidedismutase (SOD,300 U/mL),and vitamin C (1×10~(-4)mol/L).Results:Tension gen-erated 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 signifi-cantly enhanced from 35%±4% (control) to 56%±9%,60%±5%,and 49%±6% bySOD,CAT,and vitamin C,respectively (P<0.05,n=8).However,the relaxation ofET-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,whileSOD 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 hadno effect,but CAT attenuated (44%,P<0.05,n=9) the tension induced by ET-1.Conclusion:We have demonstrated that O_2~-and H_2O_2 differentially modulate BKrelaxation in an agonist-specific manner.O_2~-attenuates BK-induced relaxation ofPE contraction,but contributes to the relaxation of ET-1 contraction.O_2~-seems toinhibit PE contraction,while H_2O_2 contributes to ET-1-induced contraction.Thus,ROS differentially modulate vascular tone depending on the vasoactive agentthat is used to generate the tone. Aim: We tested the hypothesis that bradykinin (BK) -induced relaxation of phe-nylephrine (PE) and endothelin-1 (ET-1) contractions can be differentially modu- lated by reactive oxygen species 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 orET-1 (1 × 10 -9 mol / L) -induced tension was evaluated in the aorta in the presence of the following antioxidants: catalase (CAT, 300 Results: Tension gen-erated by ET-1 (1 × 10 -9 (U / mL), superoxidedismutase (SOD, 300 U / mL), and vitamin C (1 × 10 -4 mol / L) ) 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) was wasfifi-cantly enhanced f rom 35% ± 4% (control) to 56% ± 9%, 60% ± 5%, and 49% ± 6% bySOD, CAT, and vitamin C, respectively relaxation of ET-1 (1 × 10 -9 mol / L) was significantly attenuated from 75% ± 5% (control) to 37% ± 9%, 63% ± 4%, and 39% ± 7% by (P <0.05, n = 8) .On the other hand, CAT had no effect on PE-induced tension, whileSOD enhanced PE-induced tension (36%, P <0.05, n = The tension induced by PE.By contrast, SOD or vitamin C hadno effect, but CAT attenuated (44%, P <0.05, n = 9) the tension induced by ET-1.Conclusion: We have demonstrated that O_2 ~ -and H_2O_2 differentially modulate BKrelaxation in an agonist-specific manner. O_2 ~ -attenuates BK-induced relaxation of PE contraction, but contributes to the relaxation of ET-1 contraction. O_2 ~ -seems toinhibit PE contraction, while H_2O_2 contributes to ET-1-induced contraction.Thus, ROS differentially modulate vascular tone depending on the vasoactive agentthat is used to generate the tone
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