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[源自肾上腺髓质素原的肽对大鼠主动脉一氧化氮生成的影响]

[Effects of peptides originated from the proadrenomedullin on the production of nitric oxide in rat aorta].

作者信息

Dong Xianhong, Li Juxiang, Zhong Guangzhen, Ren Yongsheng, Wu Shengying, Tang Chaoshu

机构信息

Department of Physiology and Pathophysiology, Peking University School of Basic Medical Science, Beijing 100083, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Apr 18;35(2):146-9.

Abstract

OBJECTIVE

To observe the effect of adrenomedullin (ADM) on the production of nitric oxide (NO) in rat aorta and the effect of Proadrenomedullin N-terminal 20 peptide (PAMP) and adrenotensin (ADT) on the ADM-induced NO production.

METHODS

Isolated aortic tissues were exposed to ADM, PAMP and ADT for 2 h. The NO production, indicated by nitrite content in the incubated media, and the nitric oxide synthase (NOS) activity in the incubated tissues were assayed.

RESULTS

Nitrite productions and NOS activities of the aortic tissues were significantly increased by ADM in a concentration-dependent manner. The nitrite production and NOS activity of the aortic tissues stimulated by ADM (10(-8) mol.L-1) incubation were (0.282 +/- 0.046) mumol per mg protein and (0.323 +/- 0.056) pmol.min-1 per mg protein, respectively, which were greater than those of the control (0.173 +/- 0.026) mumol per mg protein and (0.110 +/- 0.028) pmol.min-1 per mg protein (P < 0.01), respectively. The nitrite production and NOS activity were (0.204 +/- 0.049) mumol per mg protein and(0.178 +/- 0.023) pmol.min-1 per mg protein when the tissues were treated with ADM (10(-8) mol.L-1) and PAMP (10(-8) mol.L-1) in combination, and were (0.150 +/- 0.036) mumol per mg protein and (0.123 +/- 0.031) pmol.min-1 per mg protein when ADM (10(-8) mol.L-1) and ADT (10(-8) mol.L-1) were used in combination, which were significantly less than those in ADM (10(-8) mol.L-1) group. After incubation of the aortic tissues with the same concentrations(10(-8) mol.L-1) of ADM, PAMP and ADT in combination, the nitrite production and NOS activity were (0.162 +/- 0.029) mumol per mg protein and (0.110 +/- 0.024) pmol.min-1 per mg protein, which were also greatly reduced as compared with those of the ADM group (10(-8) mol.L-1, P < 0.01). However, neither PAMP nor ADT had effect on the production of nitrite and NOS activity in the aortic tissues.

CONCLUSION

ADM enhanced the NO production in rat aorta, which was antagonized by PAMP and ADT alone or in combination through influencing the NOS activity.

摘要

目的

观察肾上腺髓质素(ADM)对大鼠主动脉一氧化氮(NO)生成的影响,以及前肾上腺髓质素N端20肽(PAMP)和肾上腺紧张素(ADT)对ADM诱导的NO生成的影响。

方法

将分离的主动脉组织分别用ADM、PAMP和ADT处理2小时。检测孵育介质中亚硝酸盐含量所指示的NO生成量,以及孵育组织中的一氧化氮合酶(NOS)活性。

结果

ADM可使主动脉组织中亚硝酸盐生成量和NOS活性显著增加,且呈浓度依赖性。用ADM(10⁻⁸mol·L⁻¹)孵育后,主动脉组织中亚硝酸盐生成量和NOS活性分别为(0.282±0.046)μmol/mg蛋白和(0.323±0.056)pmol·min⁻¹/mg蛋白,均显著高于对照组的(0.173±0.026)μmol/mg蛋白和(0.110±0.028)pmol·min⁻¹/mg蛋白(P<0.01)。ADM(10⁻⁸mol·L⁻¹)与PAMP(10⁻⁸mol·L⁻¹)联合处理时,亚硝酸盐生成量和NOS活性分别为(0.204±0.049)μmol/mg蛋白和(0.178±0.023)pmol·min⁻¹/mg蛋白;ADM(10⁻⁸mol·L⁻¹)与ADT(10⁻⁸mol·L⁻¹)联合处理时,亚硝酸盐生成量和NOS活性分别为(0.150±0.036)μmol/mg蛋白和(0.123±0.031)pmol·min⁻¹/mg蛋白,均显著低于ADM(10⁻⁸mol·L⁻¹)组。主动脉组织用相同浓度(10⁻⁸mol·L⁻¹)的ADM、PAMP和ADT联合孵育后,亚硝酸盐生成量和NOS活性分别为(0.162±0.029)μmol/mg蛋白和(0.110±0.024)pmol·min⁻¹/mg蛋白,与ADM组(10⁻⁸mol·L⁻¹)相比也显著降低(P<0.01)。然而,PAMP和ADT单独对主动脉组织中亚硝酸盐生成和NOS活性均无影响。

结论

ADM可增强大鼠主动脉中NO的生成,PAMP和ADT单独或联合使用可通过影响NOS活性拮抗ADM的这一作用。

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