Glucagon: endocrine effects and calcium involvement in cardiovascular actions in dogs
Chernow, B.; Reed, L.; Geelhoed, G.W.; Anderson, M.; Teich, S.; Meyerhoff, J.; Beardsley, D.; Lake, C.R.; Holaday, J.W.
Circulatory Shock 19(4): 393-407
1986
ISSN/ISBN: 0092-6213 PMID: 2427245 Document Number: 279604
Although the cardiovascular effects of glucagon are understood, its mechanism(s) of action remains unclear. We studied the effects of increasing doses of glucagon (0.001, 0.01, 0.1 mg/kg) on cardiovascular responses in dogs relative to concurrent measurements of circulating glucagon, cyclic AMP, glucose, norepinephrine, epinephrine, triiodothyronine, thyroxine, and cortisol levels. Glucagon-induced increases in plasma cyclic AMP, glucose, and catecholamine concentrations paralleled the heart rate response to glucagon administration. Further studies were conducted to evaluate the role of .beta.-adrenergic function as well as calcium in mediating glucagon's actions. The tachycardic effects of glucagon (0.01 mg/kg) were unaltered by prior .beta.-adrenergic receptor blockade with propranolol (3.5 mg/kg total dose). The calcium antagonist verapamil (0.2 mg/kg bolus then 7.5 .mu.g/kg/min/infusion) prevented glucagon-induced increases in heart rate. However, the coadministration of glucagon (0.01 mg/kg) with calcium (1.0, 5.0, 10.0, or 50.0 mg/kg) did not alter glucagon's cardiovascular effects. These data indicate that glucagon is a potent tachycardiac agent that also elevates circulating endocrine-related substances. The antagonism of glucagon's tachycardiac effects by verapamil suggests that glucagon's action may be via glucagon-induced calcium movement through calcium channels, although extracellular calcium changes do not alter glucagon's effect. Furthermore, the persistence of glucagon's cardiovascular actions following .beta.-adrenergic blockade indicates the potential clinical utility of glucagon in reversing the adverse effects of .beta.-blocker overdoses, and its potential usefulness in treating circulatory shock in "beta-blocked" patients.