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 antiadrenergic effects of adenosine and carbachol on beta-adrenoceptor-stimulated human ventricular contractility in vivo. In addition, the antiadrenergic effects of adenosine and carbachol were compared in vitro.

BACKGROUND

Adenosine is reported to exhibit an antiadrenergic negative inotropic response in the beta-adrenergic-stimulated ventricular myocardium 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 echocardiography and simultaneous blood pressure monitoring. It was calculated as the increase in the rate-corrected velocity of circumferential 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 presence of 0.03 mumol/liter of isoproterenol on cumulative concentration-response curves of isolated, electrically driven human ventricular muscle strips were compared in vitro (n = 13).

RESULTS

The positive inotropic response to continuous infusion of 20 ng/kg per min of isoproterenol (increase of rate-corrected velocity of circumferential fiber shortening [10.2 +/- 2.1% x square root of beats/min per ms] and increase of systolic pressure/dimension ratio 1.09 +/- 0.3 mm Hg/mm) was significantly (p < 0.01) reduced by 3.6 micrograms/kg body weight of intravenous carbachol (4.2 +/- 1.2% x square root of beats/min per ms, 0.21 +/- 0.18 mm Hg/mm) but not by 50 micrograms/kg of intravenous adenosine (8.2 +/- 3.1% x square root of beats/min per ms, 1.35 +/- 0.42 mm Hg/mm), although adenosine induced a significant negative dromotropic effect. In vitro comparison of force of contraction with cumulative concentration-response curves in the presence of 0.03 mumol/liter of isoproterenol demonstrated an EC50 value (concentration producing half-maximal effect) for adenosine 466 times higher than that for carbachol (65.3 vs. 0.14 mumol/liter, p < 0.001).

CONCLUSIONS

In contrast to carbachol, adenosine does not attenuate the catecholamine-induced increase in contractility in the human ventricle in vivo. These differences between the A1-adenosine receptor- and m-cholinoceptor-mediated effects could be due to fewer A1-adenosine receptors or a less efficient receptor-effector coupling, or both.