Compartmentation and hemodynamic effects of nicotine in isolated, perfused guinea pig hearts

Tachyphylaxis with respect to the positive inotropic and positive chronotropic effects of nicotine in isolated perfused hearts of guinea pigs was found to persist for 3 and 10 min, respectively, after discontinuation of intracoronary infusion of nicotine (5 X 10(-5) M). The longer duration of chronotropic tachyphylaxis correlated with a slower release of nicotine from the tissue of the right atrium in comparison to the washout from the ventricular myocardium. A similar disparity in washout between atrial and ventricular tissue was found for inulin. Thus, greater perfusion of the ventricular tissue, not a difference in affinity for nicotine, seems to account for the more rapid recovery of the inotropic response to nicotine. The apparent volume of distribution of nicotine in both atrial and ventricular myocardium was about 2 ml/g wet weight; uptake and release of nicotine was rapid. Kinetic analyses of coronary venous washout yielded four components, indicating that nicotine is distributed in at least four (kinetically defined) compartments within the ventricular myocardium. Washout from the largest tissue compartment was controlled by the rate of perfusion of the vascular space, as demonstrated by comparison with washout of erythrocytes, inulin, sucrose, and urea from the heart. Hexamethonium reduced the nicotine content of this fast-emptying compartment from 85-57 nmol/g (prelabeling concentration of nicotine 5 X 10(-5) M), giving an upper estimate for the number of specific nicotine binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)