THE EFFECTS OF GR79236 ON PLASMA FATTY-ACID CONCENTRATIONS, HEART-RATE AND BLOOD-PRESSURE IN THE CONSCIOUS RAT

GR79236 (N-[(1S,trans)-2-hydroxycyclopentyl]adenosine) is orally active adenosine A(1) receptor agonist, which decreases plasma non-esterified fatty acid levels in fasted rats. This study has quantified the effects of GR79236 on plasma non-esterified fatty acid levels, blood pressure and heart rate in conscious rats. Blood pressure and heart rate were continuously recorded in rats for 30 min before and 1 h after oral dosing with GR79236 (0.03-3 mg/kg) or vehicle. Plasma non-esterified fatty acid concentrations were determined in blood sampled before and 1 h after dosing. GR79236 produced dose-related reductions in plasma non-esterified fatty acid concentrations, with an almost maximal effect (63.2%) occurring after 1 mg/kg. This dose induced a small but significant decrease in heart rate (12.0%), and a non-significant decrease in mean brood pressure (6.3%). Thus, in the conscious rat, GR79236 can exert profound antilipolytic effects with minimal effects on blood pressure and heart rate.