ANTIADRENERGIC EFFECT OF CARBACHOL BUT NOT OF ADENOSINE ON CONTRACTILITY IN THE INTACT HUMAN VENTRICLE IN-VIVO

Objectives. The purpose of this study was to investigate the antiadren ergic effects of adenosine and carbachol on beta-adrenoceptor-stimulat ed human ventricular contractility in vivo. In addition, the antiadren ergic effects of adenosine and carbachol were compared in vitro. Backg round. Adenosine is reported to exhibit an antiadrenergic negative ino tropic response in the beta-adrenergic-stimulated ventricular myocardi um in vitro. The effect of adenosine is similar to the antiadrenergic effect of m-cholinoceptor stimulation in vitro. Methods. The inotropic response in vivo was assessed in seven healthy volunteers by M-mode e chocardiography and simultaneous blood pressure monitoring. It was cal culated as the increase in the rate-corrected velocity of circumferent ial fiber shortening and in the systolic pressure/dimension ratio. All volunteers received pretreatment with 450 mg of dipyridamole/day for 48 h. In addition, the effects of adenosine and carbachol in the prese nce of 0.03 mu mol/liter of isoproterenol on cumulative concentration- response curves of isolated, electrically driven human ventricular mus cle strips were compared in vitro (n = 13). Results. The positive inot ropic response to continuous infusion of 20 ng/kg per min of isoproter enol (increase of rate-corrected velocity of circumferential fiber sho rtening [10.2 +/- 2.1% x root beats/min per ms] and increase of systol ic pressure/dimension ratio 1.09 +/- 0.3 mm Hg/mm) was significantly ( p < 0.01) reduced by 3.6 mu g/kg body weight of intravenous carbachol (4.2 +/- 1.2% x root beats/min per ms, 0.21 +/- 0.18 mm Hg/mm) but not by 50 mu g/kg of intravenous adenosine (8.2 +/- 3.1% x root beats/min per ms, 1.35 +/- 0.42 mm Hg/mm), although adenosine induced a signifi cant negative dromotropic effect. In vitro comparison of force of cont raction with cumulative concentration-response curves in the presence of 0.03 mu mol/liter of isoproterenol demonstrated an EC(50) value (co ncentration producing half maximal effect) for adenosine 466 times hig her than that for carbachol (65.3 vs. 0.14 mu mol/liter, p < 0.001). C onclusions. In contrast to carbachol, adenosine does not attenuate the catecholamine induced increase in contractility in the human ventricl e in vivo. These differences between the A(1)adenosine receptor- and m -cholinoceptor-mediated effects could be due to fewer A(1)-adenosine r eceptors or a less efficient receptor-effector coupling, or both.