In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 93, No. 4 ( 1996-02-15), p. 763-771
Abstract:
Background The present study investigated biochemical and functional consequences of chronic activation of the inhibitory G iα -coupled adenylyl cyclase pathway in the heart. Methods and Results Rats (220 to 260 g) were treated with 4-day infusions of the M-cholinoceptor agonist carbachol (9.6 mg/kg per day) or vehicle. An additional group that received the β-adrenoceptor agonist isoprenaline (2.4 mg/kg per day) served as control. The main finding was that chronic infusion of carbachol led to a marked increase in isoprenaline- or forskolin-induced arrhythmia in electrically driven papillary muscles (in vitro). Compared with control, the potency of isoprenaline and forskolin to induce arrhythmia in cardiac preparations from carbachol-treated rats was increased 36- and 2.2-fold and the efficacy was increased 7.3- and 2.3-fold, respectively. The potency of carbachol to antagonize the isoprenaline- and forskolin-induced arrhythmia was decreased 30-fold. These changes were accompanied by a decrease in left ventricular M-cholinoceptor density by 15% ( P 〈 .05) and a decrease in pertussis toxin–sensitive G proteins (G iα ) by 26% ( P 〈 .05) without a decrease in the corresponding mRNAs. β-Adrenoceptor density and basal and stimulated adenylyl cyclase activity remained unchanged. In contrast, isoprenaline infusion induced a decrease in arrhythmogenic potency of forskolin ( P =NS), which was accompanied by a decrease in β-adrenoceptor density, an increase in G iα protein and mRNA levels, and a decrease in basal and stimulated adenylyl cyclase activity. Conclusions Chronic parasympathetic activation sensitizes the myocardium to cAMP-induced arrhythmia. These changes may be due to quantitative alterations in functional G iα .
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.93.4.763
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1996
detail.hit.zdb_id:
1466401-X
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