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Effects of Bordetella pertussis toxin pretreatment on the antiarrhythmic action of ischaemic preconditioning in anaesthetized rats
Author(s) -
Piacentini L.,
Wainwright C.L.,
Parratt J.R.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13269.x
Subject(s) - pertussis toxin , medicine , chronotropic , ventricular fibrillation , anesthesia , bordetella pertussis , ischemia , toxin , cardiology , heart rate , receptor , g protein , chemistry , biology , blood pressure , biochemistry , bacteria , genetics
1 Bordetella pertussis toxin, which catalyses the ADP‐ribosylation of certain guanine nucleotide binding proteins (G proteins), thus functionally uncoupling them from associated receptors, was examined to determine whether it modified the antiarrhythmic effect of ischaemic preconditioning in anaesthetized rats. 2 Pertussis toxin (25 μg kg −1 , i.p., 48 h prior to heart isolation) attenuated the negative chronotropic effect of acetylcholine (ACh) in rat isolated Langendorff perfused hearts. ACh (10 μ m ) reduced heart rate by 4% in hearts taken from pertussis toxin‐treated animals, compared to a reduction of 57% in hearts taken from animals treated only with vehicle. 3 In anaesthetized rats, ischaemic preconditioning (a single 3 min occlusion of the left main coronary artery followed by 10 min reperfusion) had a pronounced antiarrhythmic effect during a subsequent 30 min period of regional myocardial ischaemia. Compared to hearts receiving only a 30 min period of left coronary occlusion, there was a reduced mortality (67% and 0% for control and preconditioned groups, respectively; P <0.01) and decreased incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF). Pretreatment with pertussis toxin (25 μg kg −1 , i.p., 48 h previously) did not modify the arrhythmias associated with a 30 min period of regional myocardial ischaemia, neither did it modify the reduction in mortality (from 56% to 0%; P <0.05) associated with preconditioning. Furthermore, the decrease in total ventricular premature beat count induced by preconditioning seen in controls (from 427 ± 130 to 95 ± 45) was also seen in pertussis toxin‐treated rats (from 252 ± 190 to 57 ± 25). 4 These results suggest that receptor coupling to pertussis toxin‐sensitive G proteins is not necessary for the antiarrhythmic effect of ischaemic preconditioning in this model.