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Differential acetylcholine release mechanisms in the ischemic and non-ischemic myocardium.

Abstract：

:To understand better the pathophysiological roles of the vagal efferent system in ischemic heart diseases, we examined endogenous acetylcholine (ACh) release in the myocardium in vivo. Acute myocardial ischemia was induced in anesthetized cats by a 60-min occlusion of the left anterior descending coronary artery (LAD). We implanted dialysis probes in the left ventricular free wall and measured the dialysate ACh concentration using liquid chromatography. In the ischemic region, the ACh level increased from 0.68+/-0.12 to 12.3+/-3.3 n M (mean+/-S.E., P<0.01) by LAD occlusion. Bilateral vagotomy did not inhibit ischemia-induced ACh release (20.3+/-6.4 n M). In vagotomized animals, inhibition of the N-type Ca(2+)channel by intravenous administration of omega-conotoxin GVIA (10microg/kg) also failed to suppress ACh release (15.9+/-2.0 n M). However, the inhibition of intracellular Ca(2+)mobilization by local administration of 3,4,5-trimethoxybenzoic acid 8-(dietyl amino)-octyl ester (1 m M) suppressed ACh release (4.4+/-0.8 n M, P<0.05 compared with no pharmacological intervention). In the non-ischemic region, the ACh level increased from 1.9+/-0.4 to 6. 0+/-1.0 n M (P<0.05) by LAD occlusion, which was completely abolished by vagotomy. We concluded that ACh release in the ischemic region was mainly attributed to a local release mechanism, whereas that in the non-ischemic region depended on the presence of intact vagal activity. The local release mechanism would depend on intracellular Ca(2+)mobilization but not on N-type Ca(2+)channel opening.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Kawada T,Yamazaki T,Akiyama T,Sato T,Shishido T,Inagaki M,Takaki H,Sugimachi M,Sunagawa K

doi

10.1006/jmcc.1999.1087

keywords:

subject

Has Abstract

pub_date

2000-03-01 00:00:00

pages

405-14

issue

3

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(99)91087-8

journal_volume

32

pub_type

杂志文章

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