Effect of clonidine on blood pressure and GABAergic mechanisms in spontaneously hypertensive rats.
The action of clonidine on blood pressure and on the functional state of the gamma-aminobutyric acid-ergic (GABAergic) system was studied. A single injection of clonidine (1, 5, 10, 20 micrograms.kg-1) induced a dose-dependent decrease of blood pressure. Chronic administration of clonidine, 10 micrograms.kg-1, produced the maximum effect after the third injection. The effect was maintained for the duration of the study. Single or chronic clonidine injections, at the dose of 10 micrograms.kg-1 enhanced the GABA content in the brain and hypothalamus. This effect was less pronounced in the hippocampus. The drug administered according to the same regimen stimulated glutamic acid decarboxylase activity only in the hypothalamus. Clonidine caused a marked enhancement of specific [3H]GABA binding in the hypothalamus. These data suggest that the hypotensive action of clonidine is related to stimulation of the GABAergic system.
Czyzewska-Szafran
H
H
Department of Pharmacology, Institute of Drug Research and Control, Warsaw, Poland.
Jastrzebski
Z
Z
Remiszewska
M
M
Wutkiewicz
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013223:Statistics as Topic; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D003000:Clonidine