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 an orally active adenosine A1 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 blood pressure (6.3%). Thus, in the conscious rat, GR79236 can exert profound antilipolytic effects with minimal effects on blood pressure and heart rate.
Gardner
C J
CJ
Department of Gastrointestinal, Glaxo Group Research, Ware, Hertfordshire, UK.
Twissell
D J
DJ
Coates
J
J
Strong
P
P
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004951:Esterification; D005227:Fatty Acids / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism
D005227:Fatty Acids; D018047:Receptors, Purinergic P1; D000241:Adenosine; C082299:N-((1S,trans)-2-hydroxycyclopentyl)adenosine