THE ROLE OF ADENOSINE IN THE HYPOTENSIVE ACTIONS OF MORPHINE

The role of adenosine in the hypotensive action of morphine was examined in the pentobarbitone anaesthetized or pithed rat preparations. Adenosine (10-300 mu g/kg) induced dose-dependent decreases in diastolic blood pressure in the anaesthetized rat preparation. These effects were attenuated by infusion of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 50 mu g/kg/min), 8-phenyltheophylline (8PT; 50 mu g/kg/min), and 3,7-dimethyl-1-propargylxanthine (DMPX; 50 mu g/kg/min). In this preparation morphine (10-1000 mu g/kg) also induced dose-dependent decreases in diastolic blood pressure. Guanethidine (16 mu g/kg/min), atropine (1 mg/kg), DPCPX and 8PT reduced the effect of morphine on diastolic blood pressure, whilst DMPX (50 mu g/kg/min) was inactive. In the pithed rat preparation morphine was inactive at doses up to 10 mg/kg. The results suggest that the hypotensive effect of morphine is mediated at least in part by the release of adenosine which then acts on centrally located adenosine receptors to induce changes in autonomic control of blood pressure.