Acute effects of nicotine on hemodynamic and metabolic parameters of isolated, perfused hearts of guinea pigs and rats.
Nicotine infused in concentrations greater than 10(-6) M exerted a dose-dependent negative inotropic effect on isolated, perfused hearts of guinea pigs (Langendorff and working heart preparations). This effect became manifest after an initial positive inotropic and positive chronotropic response had subsided. Furthermore, the stimulation of cardiac contractility by norepinephrine (concentration less than 10(-7) M) was attenuated by nicotine in the guinea pig heart, but not in isolated, perfused hearts of Sprague-Dawley rats. Nicotine inhibited the positive inotropic effect of catecholamines according to the order norepinephrine greater than epinephrine greater than isoproterenol. In no case did nicotine have a marked negative chronotropic action. Changes in coronary flow, oxygen consumption, and the release of lactate and adenosine were in keeping with the state of myocardial activity in the presence of nicotine. The drug did not significantly alter myocardial uptake or release of norepinephrine during expression of its negative inotropic action. Prazosin, phentolamine, cocaine, and hexamethonium suppressed both the nicotine-induced transient stimulatory response and the negative inotropic effect in norepinephrine-stimulated hearts. In the presence of theophylline and at high perfusate calcium levels (7.5 mEqu/l) the negative inotropic effect was alleviated. The cardiodepressive action of nicotine may possibly evolve from a weak blockade of beta 1-adrenoceptors. Direct modifications of myocardial Ca2+-transport could not be observed.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D019344:Lactic Acid; D009538:Nicotine; D002118:Calcium; D009638:Norepinephrine