Enhancement of GABAergic system activity by metoprolol in spontaneously hypertensive rats.
The relevance of the GABAergic system for the antihypertensive action of metoprolol in spontaneously hypertensive rats was studied by comparing the effect of metoprolol with the effect of dihydralazine. Chronic oral treatment with metoprolol produced the maximum effect after 49 days (-delta 34 mm Hg). This effect persisted on the same level for up to 55 days. The measurements of gamma-aminobutyric acid (GABA) synthesis and specific [3H]GABA binding were performed in the hypothalamus, the pons-medulla, the hippocampus and the striatum. Significant stimulation of GABA synthesis and turnover appeared in the hypothalamus and the pons medulla. In contrast, chronic administration of dihydralazine had no influence on GABA synthesis rate. It was also shown that metoprolol elevated significantly (P < 0.01) specific [3H]GABA binding in the hypothalamus and the pons-medulla. In the striatum this effect of metoprolol was less pronounced. Binding constant analysis revealed changes in both the receptor density and affinity. Our results suggest that the hypotensive response to chronic treatment with metoprolol might be attributed to an enhancement of GABAergic system activity.
Remiszewska
M
M
Department of Pharmacology, Institute of Drug Research and Control, Warsaw, Poland.
Jastrzebski
Z
Z
Czyzewska-Szafran
H
H
Wutkiewicz
M
M
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004078:Dihydralazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D018079:Receptors, GABA / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000378:metabolism*
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D008790:Metoprolol; D004078:Dihydralazine