NICOTINE INCREASES HEART ADENOSINE RELEASE, OXYGEN-CONSUMPTION, AND CONTRACTILITY

The effect of nicotine on adenosine release, oxygen consumption, and contractility was investigated in perfused rat hearts. Continuous infusion in nicotine into the perfusing physiological saline (PS) elicited a propranolol (10-6 M) sensitive transient elevation of developed left ventricular pressure (LVP) and maximum rates of left ventricular pressure development and relaxation (.+-. dP/dtmax) within 20 s, which subsequently declined to maintained elevated plateau levels by 1 min. The continuous infusions of nicotine to achieve PS concentrations of 5 .times. 10-4, 1 .times. 10-4 M, or 5 .times. 10-5 M, respectively resulted in significant increases in the mean plateau levels of LVP (33.4, 10.1, or 6.3%), +dP/dtmax (26.3, 10.8, or 6.9%) and -dP/dtmax (35.0, 11.9, or 9.0%) at 1 min. The inclusion of propranolol (10-6 M) with or without atropine (10-6 M) with or without atropine (10-6 M) did not alter these maintained plateau responses to nicotine. During the plateau phase of the contractile response oxygen consumption of the hearts was significantly elevated by 36, 19, or 11%, and mean levels for adenosine in the coronary effluent rose by 261, 76, or 74% in response to 5 .times. 10-4, 1 .times. 10-4, or 5 .times. 10-5 M nicotine, respectively. Nicotine did not influence [14C]adenosine uptake by the hearts. These results suggest that nicotine is capable of augmenting cardiac contractility and oxygen consumption independent of .beta.-adrenergic or muscarinic influence, and elevating the appearance of adenosine in the coronary circulation presumably by enhancing myocardial production of the nucleoside.