Naloxone enhances cardiac contractile responses to epinephrine without altering epinephrine uptake from plasma.
Naloxone potentiates the inotropic effect of selected beta-agonists in the canine isolated heart. This could be accomplished by elevating circulating catecholamines through a reduction in their disposal or by the facilitation of events at or subsequent to the cardiac beta-receptor. To evaluate the first hypothesis, epinephrine was infused intravenously into a blood-perfused isolated heart-lung preparation. Catecholamines were determined and myocardial and pulmonary epinephrine uptakes were calculated. Naloxone enhanced the inotropic effect (peak +dP/dt) during epinephrine infusion. Coronary blood flow and coronary venous epinephrine concentrations were also elevated after naloxone. Calculated myocardial and pulmonary uptake of epinephrine were, however, unaltered by naloxone. The increased coronary sinus epinephrine after naloxone was evaluated further in experiments redesigned to eliminate the influence of changing coronary blood flow. Epinephrine was infused into the left common coronary and coronary blood flow as maintained constant, 100% above the resting flow rate. Naloxone enhanced the contractile response to epinephrine without altering coronary artery or coronary sinus epinephrine concentrations or myocardial epinephrine uptake. By comparison, corticosterone, an extra-neuronal uptake inhibitor, also potentiated the inotropic effect of infused epinephrine under identical conditions. However, corticosterone was accompanied by a significant increase in coronary sinus epinephrine concentration and a decrease in myocardial epinephrine uptake. We therefore concluded that the ability of naloxone to enhance the inotropic effect of epinephrine is not mediate through an increase in plasma epinephrine concentration secondary to a decrease in the disposal of circulating catecholamines.
Gu
H
H
Department of Physiology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Gaugl
J F
JF
Barron
B A
BA
Caffrey
J L
JL
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology*; D010477:Perfusion; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D009270:Naloxone; D003345:Corticosterone; D004837:Epinephrine