PRETREATMENT WITH THE DOPAMINE AGONIST QUINPIROLE INHIBITS CENTRAL ANTIHYPERTENSIVE MECHANISMS IN RATS

1. Intravenous or central treatment of spontaneously hypertensive rats (SHR) with the dopamine D-2 receptor agonist quinpirole caused a shor t-lasting presser response with little effect on heart rate, 2. At 30 min after intravenous administration of quinpirole, the antihypertensi ve effect of rilmenidine was significantly inhibited, This interaction of quinpirole and rilmenidine was similarly observed when quinpirole was administered either intravenously (0.3 or 0.1 mg/kg), in the later al cerebral ventricles (0.1 mg/kg) or intracisternally (0.1 mg/kg) or when rilmenidine was administered intravenously (1 mg/kg) or intracist ernally (0.1 mg/kg), 3. The apparent desensitization to the antihypert ensive effect of rilmenidine 30 min after pre treatment with quinpirol e was not observed after a 4 or 24 h interval. 4, These data suggest t hat quinpirole has prolonged effects on central sympathetic vasomotor mechanisms that are the target of centrally acting antihypertensive dr ugs, These and previous results show a functional interaction between central dopamine D-2 receptor activation and sympathetic responses med iated by a wide range of different receptors, including imidazoline an d 5-hydroxytryptamine 5-HT1A-receptors and alpha(2)-adrenoceptors.