IngentaConnect Endothelin-1-mediated coronary vasoconstriction deteriorates myoc...

Authors: Jie Tu¹; Qixian Shan¹; Hongfeng Jin¹; Jean-Pierre Bourreau²; Qiang Xia¹

Source: Clinical and Experimental Pharmacology and Physiology, Volume 31, Number 9, September 2004 , pp. 571-574(4)

Abstract:

Summary

1. The aim of the present study was to evaluate the contribution of disturbance of coronary perfusion to myocardial depression in hearts isolated from lipopolysaccharide (LPS)-treated rats and to investigate the involvement of endothelin (ET)-1 and nitric oxide (NO).

2. Rats were treated with LPS (10 mg/kg, i.p.) and, 4 h later, plasma ET-1 concentrations were measured by radioimmunoassay and hearts were excised for perfusion at a constant perfusion flow. The selective ET_A receptor antagonist BQ-123, in the absence or presence of aminoguanidine, a specific inhibitor of inducible NO synthase, was given 15 min before LPS challenge. Coronary perfusion pressure (CPP) and measures of myocardial contractile function were recorded.

3. In hearts isolated from LPS-treated rats, there was a marked increase in CPP that was abolished by pretreatment with BQ-123. In parallel, an increase in plasma ET-1 concentrations was seen in these rats. Lipopolysaccharide also induced decreases in left ventricular developed pressure (LVDP), the product of LVDP and heart rate and maximal rate of rise/fall of left ventricular pressure (+/– dP/dt_max). Single treatment with BQ-123 or aminoguanidine attenuated LPS-induced myocardial depression. However, when these two drugs were given simultaneously, myocardial depression elicited by LPS was blocked significantly.

4. Endothelin-1-mediated coronary vasoconstriction, together with NO, contributes to myocardial depression in hearts isolated from LPS-treated rats.

Keywords: coronary perfusion pressure; endothelin; lipopolysaccharide; myocardial depression; nitric oxide

Document Type: Research article

DOI: 10.1111/j.1440-1681.2004.04049.x

Affiliations: 1: Department of Physiology, Zhejiang University School of Medicine, Hangzhou and 2: Department of Physiology, The University of Hong Kong, Hong Kong SAR, China

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Endothelin-1-mediated coronary vasoconstriction deteriorates myocardial depression in hearts isolated from lipopolysaccharide–treated rats: Interaction with nitric oxide