Clonidine action in spontaneously hypertensive rats (SHR) depends on the GABAergic system function.
The effect of gamma-aminobutyric acid (GABA)A antagonists (bicuculline, picrotoxin) on clonidine hypotension in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were examined. The GABA turnover changes after clonidine injection in both strains were also studied. Administration of clonidine alone induced the stronger decrease of systolic blood pressure (SBP) in SHR. Co-dosage of clonidine with these agents reduced its hypotensive effect in dose dependent manner and the effectiveness of both antagonists was higher in SHR. We find that clonidine stimulates GABA synthesis in the hypothalamus and the pons-medulla in both strains but the GABA turnover rate is significantly slower in SHR. Therefore, the differences in inhibitory action of GABAA receptor antagonists between WKY and SHR rats may be explained by central GABAergic system dysfunction in the hypertension. Our results indicate that the down regulation of the GABAergic system observed in hypertension may be compensated by the action of clonidine.
Goźlińska
B
B
Department of Pharmacology, Drug Institute, Warsaw, Poland.
Czyzewska-Szafran
H
H
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects; D008526:Medulla Oblongata / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D011149:Pons / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000959:Antihypertensive Agents; D001640:Bicuculline; D003000:Clonidine; D018756:GABA Antagonists; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid