Adenosine inhibits the positive chronotropic and inotropic responses to norepinephrine and Bay k 8644 in the isolated, blood-perfused dog atrium.

We investigated the effects of adenosine on the positive chronotropic and inotropic responses to an endogenous catecholamine (norepinephrine), a beta 1-adrenoceptor agonist (dobutamine), an adenylate cyclase activator (forskolin), a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, IBMX) and a calcium channel agonist (Bay k 8644) in the isolated, blood-perfused dog atrium. Each drug was injected into the sinus node artery of the isolated atrium. Adenosine infusions at low (45 or 90 nmol/min) and high (184 or 450 nmol/min) doses induced a dose-dependent decrease of sinus rate and atrial contractile force. The positive chronotropic and inotropic responses to norepinephrine, dobutamine and forskolin were dose-dependently depressed by adenosine. IBMX- and Bay k 8644-induced positive cardiac responses were also inhibited by adenosine at high doses but not at low doses. These results suggest that adenosine attenuates calcium channel-dependent as well as cyclic AMP-dependent positive chronotropic and inotropic responses to cardiostimulants in the isolated dog atrium.