The role of adenosine in the hypotensive action of morphine was examin
ed in the pentobarbitone anaesthetized or pithed rat preparations. Ade
nosine (10-300 mu g/kg) induced dose-dependent decreases in diastolic
blood pressure in the anaesthetized rat preparation. These effects wer
e 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 preparati
on 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 bloo
d pressure, whilst DMPX (50 mu g/kg/min) was inactive. In the pithed r
at preparation morphine was inactive at doses up to 10 mg/kg. The resu
lts suggest that the hypotensive effect of morphine is mediated at lea
st in part by the release of adenosine which then acts on centrally lo
cated adenosine receptors to induce changes in autonomic control of bl
ood pressure.