两种不同慢性心力衰竭模型中的内皮依赖性舒张及异波帕明的作用。

Endothelium dependent relaxation in two different models of chronic heart failure and the effect of ibopamine.

作者信息

Buikema H, van Gilst W H, van Veldhuisen D J, de Smet B J, Scholtens E, Lie K I, Wesseling H

机构信息

Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands.

出版信息

Cardiovasc Res. 1993 Dec;27(12):2118-24. doi: 10.1093/cvr/27.12.2118.

DOI:10.1093/cvr/27.12.2118

PMID:8313417

Abstract

OBJECTIVES

The purpose was to relate endothelium dependent relaxation to neurohumoral and haemodynamic changes in rats with chronic heart failure.

METHODS

Rats were submitted to either coronary ligation causing myocardial infarction or banding of the abdominal aorta (aortic stenosis), and comparisons were made with normal rats (n = 20 per group). Starting six weeks after surgery, half of the experimental animals received ibopamine and the other half served as controls and were given saline for another three weeks. After this, haemodynamic and neurohumoral variables were determined and the rats were killed. Rings of both the thoracic and abdominal aorta were studied in organ baths to measure their response to vasoactive agents.

RESULTS

Increased plasma noradrenaline concentrations in rats with myocardial infarction and aortic stenosis were reduced by ibopamine. Blood pressure and heart rate, which were higher in rats with aortic stenosis than in rats with myocardial infarction and in normal rats, were unaffected by ibopamine. The maximal relaxation to sodium nitrite was depressed in the thoracic aorta from rats with myocardial infarction. The pIC50 of metacholine induced relaxation was smaller in the thoracic aorta from rats with myocardial infarction and aortic stenosis. By contrast, both pIC50 and the maximal relaxation (Emax) were increased in the abdominal aorta from rats with aortic stenosis, whereas Emax was smaller in rats with myocardial infarction. Ibopamine had no significant effects on these responses.

CONCLUSIONS

Endothelium dependent relaxation to metacholine was selectively altered in rats with chronic heart failure due to aortic stenosis, probably because of differences in regional haemodynamics. In rats with myocardial infarction, however, endothelium dependent relaxation was impaired in both the thoracic and abdominal aorta. Ibopamine acted as a neurohumoral modulator by reducing increased noradrenaline concentrations but had no significant effect on either endothelium dependent or independent relaxation.

摘要

目的

本研究旨在探讨慢性心力衰竭大鼠内皮依赖性舒张功能与神经体液及血流动力学变化之间的关系。

方法

将大鼠分为两组，一组进行冠状动脉结扎导致心肌梗死，另一组进行腹主动脉缩窄（主动脉狭窄），并与正常大鼠（每组20只）进行比较。术后六周开始，一半实验动物给予异波帕明，另一半作为对照给予生理盐水，持续三周。之后，测定血流动力学和神经体液变量，并处死大鼠。在器官浴中研究胸主动脉和腹主动脉环，以测量它们对血管活性药物的反应。

结果

异波帕明降低了心肌梗死和主动脉狭窄大鼠血浆去甲肾上腺素浓度的升高。主动脉狭窄大鼠的血压和心率高于心肌梗死大鼠和正常大鼠，而异波帕明对其无影响。心肌梗死大鼠胸主动脉对亚硝酸钠的最大舒张反应降低。心肌梗死和主动脉狭窄大鼠胸主动脉中乙酰甲胆碱诱导舒张的pIC50较小。相比之下，主动脉狭窄大鼠腹主动脉的pIC50和最大舒张反应（Emax）均增加，而心肌梗死大鼠的Emax较小。异波帕明对这些反应无显著影响。