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 D2 receptor agonist quinpirole caused a short-lasting pressor response with little effect on heart rate. 2. At 30 min after intravenous administration of quinpirole, the antihypertensive 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 lateral cerebral ventricles (0.1 mg/kg) or intracisternally (0.1 mg/kg) or when rilmenidine was administered intravenously (1 mg/kg) or intracisternally (0.1 mg/kg). 3. The apparent desensitization to the antihypertensive effect of rilmenidine 30 min after pretreatment with quinpirole was not observed after a 4 or 24 h interval. 4. These data suggest that quinpirole has prolonged effects on central sympathetic vasomotor mechanisms that are the target of centrally acting antihypertensive drugs. These and previous results show a functional interaction between central dopamine D2 receptor activation and sympathetic responses mediated by a wide range of different receptors, including imidazoline and 5-hydroxytryptamine 5-HT1A-receptors and alpha 2-adrenoceptors.
van den Buuse
M
M
Baker Medical Research Institute, Prahran, Victoria, Australia. maarten.vandenbuuse@baker.edu.au
Tritton
S B
SB
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles; D002946:Cisterna Magna; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010080:Oxazoles / Q000494:pharmacology; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D000077769:Rilmenidine
D000959:Antihypertensive Agents; D018491:Dopamine Agonists; D004343:Drug Implants; D010080:Oxazoles; D019257:Quinpirole; D000077769:Rilmenidine