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 compar ing the effect of metoprolol with the effect of dihydralazine. Chronic oral treatment with metoprolol produced the maximum effect after 49 d ays (-Delta 34 mm Hg). This effect persisted on the sam level for up t o 55 days. The measurements of gamma-aminobutyric acid (GABA) synthesi s and specific [H-3]GABA binding were performed in the hypothalamus, t he pons-medulla, the hippocampus and the striatum. Significant stimula tion of GABA synthesis and turnover appeared in the hypothalamus and t he pens medulla. In contrast, chronic administration of dihydralazine had no influence on GABA synthesis rate. It was also shown that metopr olol elevated significantly (P<0.01) specific [H-3]GABA binding in the hypothalamus and the pons-medulla. In the striatum this effect of met oprolol was less pronounced. Binding constant analysis revealed change s 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.