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Modulation by pertussis toxin of salbutamol- and arecoline-induced effects in the isolated heart and aorta of the rat
Authors:Wim Vleeming   Johan Wemer   Jan Riezebos   Jan G. C. Van Amsterdam   Dick J. De Wildt  Arijan J. Porsius
Affiliation:

a Faculty of Pharmacy, University Utrecht, Utrecht, Netherlands

b National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands

Abstract:The modulatory effects of pertussis toxin pretreatment on responses mediated via β-adrenoceptors and muscarinic acetylcholine receptors were investigated in isolated rat hearts and aortic rings 4 days after in vivo administration of pertussis toxin. In isolated hearts, pertussis toxin increased heart weight and baseline coronary flow values but did not effect baseline left ventricular pressure values. In unpaced hearts, pertussis toxin inhibited the arecoline-induced cardiac standstill, while in paced hearts, the β2-adrenoceptor agonist salbutamol produced a dose-dependent vasodilation with similar characteristics in pertussis toxin and control preparations. Pertussis toxin had no effect on myocardial or aortic cyclic nucleotide levels and the myocardial β-adrenoceptor density (Bmax) and dissociation constant (Kd). In precontracted aortic rings, pertussis toxin had no effect on the salbutamol or arecoline induced vasorelaxation. In summary, we demonstrated a reduced cholinergic responsiveness in isolated hearts but an intact β2-adrenoceptor pathway in isolated hearts as well as in isolated aortic rings after pertussis toxin pretreatment. In aortic rings no change in muscarinic acetylcholine receptor responsiveness occurred.
Keywords:Pertussis toxin   Salbutamol   Arecoline   Aorta   β-Adrenoceptor   Langendorff   (Rat)
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