© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Role of basal nitric oxide synthesis in vasoconstrictor hyporeactivity in the perfused rat hindlimb after myocardial infarction: effect of captopril
Department of Pharmacology, Cardiovascular Research Institute Maastricht, Universiteit Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands
* Corresponding author. Tel.: +31-43-388-1417; fax: +31-43-367-0940 D.Ceiler{at}Farmaco.Unimaas.nl
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 (
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 µM indomethacin were not different between sham and MI rats. Vasoconstrictor responses to K+ and 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 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.
KEYWORDS Heart failure; Myocardial infarction; Vasoconstriction; Endothelium-derived factors
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