GLUCAGONS CHRONOTROPIC ACTION IS CALCIUM DEPENDENT

  • 1 June 1987
    • journal article
    • research article
    • Vol. 241  (3) , 833-837
Abstract
Evidence in increasing that many anesthetics and cardiovascular agents alter cellular Ca kinetics and flux. In prior work we demonstrated that the tachycardic effects of glucagon were significantly blunted by Ca channel blockade, but not by beta adrenergic receptor blockade. Thus, the chronotropic effects of glucagon may be dependent upon extracellular Ca levels. Based upon these observations, we tested the hypothesis that changes in circulating ionized Ca concentrations may alter glucagon''s ability to increase heart rate in rats. In conscious normocalcemic rats, glucagon''s tachycardiac actions were dose related with peak effects obtained at 1 to 2 min and persisting approximately 10 min after 1.0 mg/kg of glucagon. The effects of altered Ca levels on glucagon tachycardia were evaluated in three groups of rats: 1) rats rendered hypercalcemic by the infusion of Ca chloride (10, 50 or 100 mg/ml/hr); 2) rats rendered hypocalcemic by infusion of the Ca chelator EDTA (15 or 30 mg/ml/hr); and 3) normocalcemic rats infused with saline. Normocalcemic rats had a mean ionized Ca level of 4.73 mg/dl. In rats, increasing Ca chloride doses resulted in increasing mean serum ionized Ca levels (5.24, 8.35 and 15.2 mg/dl, respectively), whereas increasing doses of EDTA produced progressive decreases in mean ionized Ca (3.62 and 2.13 mg/dl, respectively). Severe hypo (2.13 mg/dl)- or hypercalcemia (15.2 mg/dl) significantly blunted glucagon''s chronotrophic action (51 and 44%, respectively). From these data, we conclude that glucagon has its maximal tachycardiac action at physiologic Ca levels (being blunted by both hyper- and hypocalcemia), indicating that this effect of glucagon is Ca dependent. These findings further support the concept that normal circulating ionized Ca concentrations may be requisite for full responsivity to calcium-dependent medications in the critical care setting.