基础一氧化氮合成在心肌梗死后灌注大鼠后肢血管收缩反应性降低中的作用：卡托普利的影响

Role of basal nitric oxide synthesis in vasoconstrictor hyporeactivity in the perfused rat hindlimb after myocardial infarction: effect of captopril.

作者信息

Ceiler D L, Nelissen-Vrancken M, De Mey J G, Smits J F

机构信息

Department of Pharmacology, Cardiovascular Research Institute Maastricht, Universiteit Maastricht, The Netherlands.

出版信息

Cardiovasc Res. 1999 Aug 15;43(3):779-87. doi: 10.1016/s0008-6363(99)00147-9.

DOI:10.1016/s0008-6363(99)00147-9

PMID:10690350

Abstract

OBJECTIVES

The contribution of vascular changes to the development of heart failure is largely unknown. In the present study, we evaluated endothelial and vascular contractile function in the rat hindlimb vascular bed after myocardial infarction (MI), including the modulatory role of basal nitric oxide (NO) production and the effects of treatment with the angiotensin converting enzyme inhibitor captopril on vascular function.

METHODS

MI was induced in male Wistar rats by ligation of the left coronary artery. Acetylcholine-induced dilatations were assessed in the ex vivo perfused hindlimb at various time points. At 2 and 5 weeks post-MI, vascular contractile function in the perfused hindlimb was assessed from resistance changes induced by 35 mM and 125 mM potassium (K+) and the maximum increase in resistance (delta Rmax, 125 mM K+ and 3 mg phenylephrine). Basal NO synthesis was blocked for 2 weeks with L-nitro-arginine methylester (L-NAME) in sham and MI rats and similar contractility experiments were performed. The effect of captopril treatment from 2 to 5 weeks post-MI on vasoconstrictor responses was also tested.

RESULTS

Acetylcholine-induced dilatations in the presence of 10 microM indomethacin were not different between sham and MI rats. Vasoconstrictor responses to K+ and delta Rmax were reduced at 2 weeks after MI. This reduction in vasoconstrictor ability was similar to that seen in L-NAME-treated sham rats, while chronic L-NAME treatment did not affect vasoconstrictor reactivity in MI rats. Similarly, L-NAME induced an increase in mean arterial pressure in sham rats, but not in MI rats. At 5 weeks after MI, vasoconstriction to 125 mM K+ and delta Rmax were still reduced in MI rats; this response was however partially restored after captopril treatment.

CONCLUSION

The development of vascular contractile hyporeactivity in the rat hindlimb after MI may be due to reduced basal NO production. Delayed treatment with captopril improves peripheral vascular contractile function in this setting.

摘要

目的

血管变化对心力衰竭发展的作用在很大程度上尚不清楚。在本研究中，我们评估了心肌梗死（MI）后大鼠后肢血管床的内皮和血管收缩功能，包括基础一氧化氮（NO）产生的调节作用以及血管紧张素转换酶抑制剂卡托普利治疗对血管功能的影响。

方法

通过结扎左冠状动脉在雄性Wistar大鼠中诱导MI。在不同时间点对离体灌注的后肢评估乙酰胆碱诱导的扩张。在MI后2周和5周，根据35 mM和125 mM钾（K +）诱导的阻力变化以及阻力的最大增加（δRmax，125 mM K +和3 mg去氧肾上腺素）评估灌注后肢的血管收缩功能。在假手术组和MI大鼠中用L-硝基-精氨酸甲酯（L-NAME）阻断基础NO合成2周，并进行类似的收缩性实验。还测试了MI后2至5周卡托普利治疗对血管收缩反应的影响。

结果

在存在10 microM吲哚美辛的情况下，假手术组和MI大鼠之间乙酰胆碱诱导的扩张没有差异。MI后2周对K +和δRmax的血管收缩反应降低。这种血管收缩能力的降低与L-NAME处理的假手术组大鼠相似，而慢性L-NAME处理不影响MI大鼠的血管收缩反应性。同样，L-NAME诱导假手术组大鼠平均动脉压升高，但不影响MI大鼠。MI后5周，MI大鼠对125 mM K +和δRmax的血管收缩仍降低；然而，卡托普利治疗后这种反应部分恢复。