Effect of the dopamine D2 receptor agonist quinpirole on the in vivo release of dopamine in the caudate nucleus of hypertensive rats.
Using an in vivo microdialysis method, we found that the extracellular concentrations of dopamine and its main metabolite dihydroxyphenylacetic acid (DOPAC) were lower in the caudate nucleus of 8-week-old spontaneously hypertensive rats (SHR) than in the same area of age-matched normotensive Wistar-Kyoto rats (WKY). No differences in the extracellular concentrations of dopamine and DOPAC were found between renal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats when compared to their respective controls. After subcutaneous administration of the dopamine D2 receptor agonist quinpirole (10, 33 and 100 micrograms/kg), the amount of dopamine and DOPAC in the dialysates was diminished dose dependently. The quinpirole-mediated inhibition of dopamine release was more pronounced in SHR than in WKY, whereas inhibition of the extracellular DOPAC concentration was not different. Compared to WKY, the dose-response curve for the inhibition of dopamine release by quinpirole was shifted to the left in SHR and the maximal inhibition in response to the highest dose was significantly greater. Renal and DOCA-salt hypertensive rats showed no differences in the quinpirole-induced inhibition of the extracellular concentrations of striatal dopamine and DOPAC compared to their controls. The present findings on changes in dopaminergic neurotransmission and D2 autoreceptor-mediated modulation of dopamine release in genetically hypertensive rats but not in rats with experimentally induced hypertension provide further evidence for the hypothesis that alterations in the nigrostriatal dopamine system may be involved in the initiation of the development of spontaneous hypertension.
Linthorst
A C
AC
Rudolf Magnus Institute, Department of Pharmacology, Medical Faculty, State University of Utrecht, The Netherlands.
De Lang
H
H
De Jong
W
W
Versteeg
D H
DH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002421:Caudate Nucleus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000494:pharmacology; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D019257:Quinpirole; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D009435:Synaptic Transmission / Q000187:drug effects
D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D003900:Desoxycorticosterone; D004298:Dopamine