Protective effects of adrenoceptor-blocking agents on myocardial injury induced by epinephrine in mice.
Employing propranolol as a non-selective beta-blocker, atenolol, acebutolol and metoprolol as selective beta 1-blockers, butoxamine as a selective beta 2-blocker, labetalol as an alpha- and beta-blocker, and phentolamine as an alpha-blocker, we compared the effects of these adrenoceptor-blocking agents to reduce the degree of the myocardial injury induced by epinephrine in mice. Epinephrine in a single dose of 4 mg/kg/day, s.c., daily for 7 days, caused widely extended lesions, necrosis and fibrosis in the myocardial fibers, and degeneration in the residual myocardial fibers. The adrenoceptor-blocking agents in a dose of 10 mg/kg/day, s.c., given 30 minutes prior to epinephrine to each mouse daily for 7 days, had reduced the degree of the myocardial injury induced by epinephrine. The blockers, all, effectively suppressed the injury. Although metoprolol and butoxamine were less effective on the protection of the cardiotoxicity than phentolamine, the other blockers prevented the cardiotoxicity with the same degree as phentolamine did. These findings suggest that not only alpha- but also beta 1- and beta 2-adrenoceptors play critical roles in producing the myocardial injury.
Kubota
T
T
Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Yamazaki
N
N
Sudo
J
J
Monma
Y
Y
Kaku
T
T
Okuyama
T
T
Tanabe
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004837:Epinephrine / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004837:Epinephrine