CARDIOVASCULAR EFFECTS OF THE BENZODIAZEPINE RECEPTOR PARTIAL INVERSEAGONIST FG-7142 IN RATS

Effects of the benzodiazepine receptor (BZR) partial inverse agonist F G 7142 (FG) on basal and reactive cardiovascular measures were examine d in Freely moving rats. FG (8 mg/kg) modestly increased basal heart p eriod, but had no effects on basal blood pressure. More notably, howev er, FG augmented the cardioacceleratory response to an auditory stimul us relative to vehicle controls. Selective blockade of sympathetic (at enolol, 1 mg/kg) or parasympathetic (scopolamine methylnitrate, 0.1 mg /kg) effects on the heart under control conditions revealed that the s timulus-evoked cardiac response originated from a concurrent (reciproc al) sympathetic activation and vagal withdrawal. Following FG pretreat ment, both atenolol and scopolamine blocked the cardioacceleratory res ponse to the auditory stimulus. Thus, although FG minimally increased basal heart period, FG significantly enhanced a reactive cardioacceler ation. More importantly, these results demonstrate that the cardiovasc ular effects of BZR inverse agonists are more fully characterized by a n assessment of both tonic and reactive cardiovascular responses.