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[过氧亚硝酸盐对兔肺动脉体外反应性的影响]

[Effect of peroxynitrite on the reactivity of rabbit pulmonary arteries in vitro].

作者信息

Gu Zhen-Yong, Ling Yi-Ling, Xu Xiao-Hu, Meng Ai-Hong, Li Shu-Jin

机构信息

Shantou University Medical College, Shantou 515031.

出版信息

Sheng Li Xue Bao. 2003 Aug 25;55(4):469-74.

Abstract

To investigate the effect of peroxynitrite (ONOO(-)) on the reactivity of rabbit pulmonary artery, the responses of rabbit pulmonary artery rings (PARs) pre-incubated with ONOO(-) to endothelium-dependent and receptor-dependent relaxants ACh and ADP, endothelium-dependent and receptor-independent relaxant calcium ionophore A23187, endothelium-independent relaxant sodium nitroprusside (SNP) and alpha(1)-adrenoceptor agonist phenylephrine (PE) were observed in vitro in an accumulative manner. (1) Relaxations of PARs to ACh, calcium ionophore A23187 and ADP were markedly impaired with shift of accumulative dose-response curve of each agonist to the right. Inhibition of endothelium-dependent and receptor-dependent or independent relaxation by ONOO(-) was dose-dependent. (2) ONOO(-) incubation inhibited SNP-induced relaxation in a dose-dependent manner. (3) Contractile response of PARs to PE varied with the different doses of ONOO(-). In PARs pre-incubated with 0.5 mmol/L ONOO(-), contractile response was significantly enhanced with shift of PE accumulative dose-response curve to the left, whereas in PARs pre-incubated with 1.0 mmol/L or 2.0 mmol/L ONOO(-), it was markedly reduced with right shift of PE accumulative dose-response curve. (4) Vehicle of ONOO(-) had no effect on responses to each agonist.Decomposed ONOO(-) had minimal effect on the response to PE and ADP, in contrast, relaxation of PARs to ACh, A23187 and SNP were enhanced. These results indicate that ONOO(-) may contribute to regulatory disorder of pulmonary artery reactivity.

摘要

为研究过氧亚硝酸盐(ONOO⁻)对兔肺动脉反应性的影响,采用累积给药法在体外观察预先用ONOO⁻孵育的兔肺动脉环(PARs)对内皮依赖性和受体依赖性舒张剂乙酰胆碱(ACh)和二磷酸腺苷(ADP)、内皮依赖性和受体非依赖性舒张剂钙离子载体A23187、非内皮依赖性舒张剂硝普钠(SNP)以及α₁肾上腺素能受体激动剂去氧肾上腺素(PE)的反应。(1)PARs对ACh、钙离子载体A23187和ADP的舒张反应明显受损,各激动剂的累积剂量 - 反应曲线均右移。ONOO⁻对内皮依赖性和受体依赖性或非依赖性舒张的抑制呈剂量依赖性。(2)ONOO⁻孵育以剂量依赖性方式抑制SNP诱导的舒张。(3)PARs对PE的收缩反应随ONOO⁻剂量不同而变化。在预先用0.5 mmol/L ONOO⁻孵育的PARs中,收缩反应显著增强,PE累积剂量 - 反应曲线左移;而在预先用1.0 mmol/L或2.0 mmol/L ONOO⁻孵育的PARs中,收缩反应明显减弱,PE累积剂量 - 反应曲线右移。(4)ONOO⁻的溶剂对各激动剂的反应无影响。分解的ONOO⁻对PE和ADP的反应影响极小,相反,PARs对ACh、A23187和SNP的舒张增强。这些结果表明,ONOO⁻可能导致肺动脉反应性调节紊乱。

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