Cardiovascular effects of the benzodiazepine receptor partial inverse agonist FG 7142 in rats

Effects of the benzodiazepine receptor (BZR) partial inverse agonist FG 7142 (FG) on basal and reactive cardiovascular measures were examined in freely moving rats. FG (8 mg/kg) modestly increased basal heart period, but had no effects on basal blood pressure. More notably, however, FG augmented the cardioacceleratory response to an auditory stimulus relative to vehicle controls. Selective blockade of sympathetic (atenolol, 1 mg/kg) or parasympathetic (scopolamine methylnitrate, 0.1 mg/kg) effects on the heart under control conditions revealed that the stimulus-evoked cardiac response originated from a concurrent (reciprocal) sympathetic activation and vagal withdrawal. Following FG pretreatment, both atenolol and scopolamine blocked the cardioacceleratory response to the auditory stimulus. Thus, although FG minimally increased basal heart period, FG significantly enhanced a reactive cardioacceleration. More importantly, these results demonstrate that the cardiovascular effects of BZR inverse agonists are more fully characterized by an assessment of both tonic and reactive cardiovascular responses.