Enhanced in vivo and in vitro contractile responses to beta(2)-adrenergic receptor stimulation in dogs susceptible to lethal arrhythmias.
The response to beta-adrenergic receptor (beta-AR) stimulation was evaluated in both isolated cardiomyocytes (video edge detection) and the intact animal (echocardiography) in dogs either susceptible (S) or resistant (R) to ventricular fibrillation induced by a 2-min coronary occlusion during the last minute of exercise. In the intact animal, velocity of circumferential fiber shortening (Vcf) was evaluated both before (n = 27, S = 12 and R = 15) and after myocardial infarction. Before infarction, increasing doses of isoproterenol provoked similar contractile and heart rate responses in each group of dogs. Either beta(1)-AR (bisoprolol) or beta(2)-AR (ICI-118551) antagonists reduced the isoproterenol response, with a larger reduction noted after the beta(1)-AR blockade. In contrast, after infarction, isoproterenol induced a significantly larger Vcf and heart rate response in the susceptible animals that was eliminated by beta(2)-AR blockade. The single-cell isotonic shortening response to isoproterenol (100 nM) was also larger in cells obtained from susceptible compared with resistant dogs and was reduced to a greater extent by beta(2)-AR blockade in the susceptible dog myocytes (S, -48%, n = 6; R, -15%, n = 9). When considered together, these data suggest that myocardial infarction provoked an enhanced beta(2)-AR response in susceptible, but not resistant, animals.
Houle
M S
MS
Department of Physiology and Cell Biology, The Ohio State University, 1645 Neil Ave., Columbus, OH 43210, USA.
Altschuld
R A
RA
Billman
G E
GE
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D017298:Bisoprolol / Q000494:pharmacology; D004285:Dogs; D004452:Echocardiography; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology; D011412:Propanolamines / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000503:physiopathology
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C026777:ICI 118551; D007545:Isoproterenol; D017298:Bisoprolol