Does endogenous adenosine have a role in the cardiac responses to isoprenaline and in the rapid fade of the inotropic response of perfused heart?

Abstract

The role of endogenous adenosine during the beta-adrenoceptor responses to isoprenaline of guinea-pig isolated cardiac preparations was examined. Insignificant effects of adenosine deaminase (0.3 U.mL-1) on cumulative concentration--response curves for isoprenaline on isolated left and right atria and papillary muscles indicated a negligible depressant effect of endogenous adenosine during these responses. The increase in force of contraction to an infusion of isoprenaline (14 nM) in perfused spontaneously beating hearts rapidly waned while the infusion continued, whereas the increase in rate of contraction remained constant throughout the infusion. The degree of fade was less in paced preparations (5 Hz), indicating that it was only in part due to the rate increase exerting some mechanical constraint on the force of contraction. The P1-purinoceptor antagonist 8-phenyltheophylline (12 microM) and adenosine deaminase (0.3 U.mL-1) did not enhance the peak responses to the isoprenaline infusion. The fade of the inotropic response in both spontaneous and paced hearts was also not attenuated by the presence of 8-phenyltheophylline or adenosine deaminase. The fade was not, therefore, due to release of endogenous adenosine exerting a depressant effect. Whether this declining inotropic response represents a form of rapid desensitization remains to be determined.