ADENOSINE AL RECEPTOR AGONIST GR79236 SUPPRESSES APNEA DURING ALL SLEEP STAGES IN THE RAT

We tested the hypothesis that N-[(1S, trans)-2-hydroxycyclopentyl]aden osine (GR79236), a novel adenosine A1 receptor agonist, would suppress sleep-related apnea in the rat at doses nor associated with hypotensi on or hypothermia. Nine adult Sprague-Dawley rats were instrumented fo r chronic recording of sleep by electroencephalographic and electromyo graphic monitoring. Respirations were measured by single chamber pleth ysmograph, and blood pressure and heart period were transduced by a te lemetric implant. Each rat was polygraphically recorded for 6 hours on four occasions in random order, with recordings for an individual ani mal separated by at least 3 days. Fifteen minutes prior to each record ing (0945 hours) each animal received a 1 ml/kg intraperitoneal bolus injection of one of four injectates: saline (control) or 0.03 mg/kg, 0 .3 mg/kg, or 3 mg/kg of GR79236. The study was a repeated-measures bal anced design such that each animal was recorded exactly once for each injectate. The rate of spontaneous apneas (pauses > 2.5 seconds) was s ignificantly reduced during all sleep stages by all doses of GR79236. At the highest dose, apnea index was reduced by over 70% in both non-r apid eye movement (NREM) and rapid eye movement (REM) sleep. In contra st, GR79236 had no effect on sleep stage volumes or blood pressure at any dose tested. Heart rate and core temperature were reduced only at the highest dose (3 mg/kg). We conclude that the adenosine A1 receptor agonist GR79236 significantly suppresses apnea expression in all slee p stages at doses not associated with significant changes in sleep arc hitecture, blood pressure, heart rate, or core temperature.