The responsiveness of D1- and D2-dopamine receptors in the striatum and hypothalamus of spontaneous and vasopressin hypertensive rats.
Low doses of apomorphine (20-50 micrograms/kg) induced an increase in the activity of an endogenous inhibitor of cAMP dependent protein Kinases (type I inhibitor) in the striatum, anterior and posterior hypothalamus of normotensive rats by stimulating D2-dopamine receptors. In contrast, high doses of the compound (2-10 mg/kg) produced a dose dependent decrease in type I inhibitor activity. In the posterior hypothalamus of vasopressin hypertensive rats and SHR the maximal increase of type I inhibitor activity was markedly higher than in normotensive animals. Moreover, apomorphine induced the increase of type I inhibitor activity in a much wider range of doses. Only as high dose of the compound as 10 mg/kg was able to decrease type I inhibitor activity. This points to a marked supersensitivity of D2 receptors and suggests the subsensitivity of D1 receptors in this brain area of hypertensive rats. In contrast, in the striatum and anterior hypothalamus of hypertensive rats the apomorphine dose response curves were similar to those in normotensive rats. Thus, it seems tha hypertension is associated with the alteration in sensitivity of D2 and D1 receptors in the posterior hypothalamus, the brain area involved in regulation of blood pressure.
Szmigielska
H
H
Department of Pharmacodynamics, Medical Academy, Lódź, Poland.
Szmigielski
A
A
Szadowska
A
A
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000378:metabolism; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000378:metabolism; D008297:Male; D047428:Protein Kinase Inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D014667:Vasopressins
D047428:Protein Kinase Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014667:Vasopressins