GABA(B) RECEPTOR-MEDIATED MECHANISMS IN THE RVLM STUDIED BY MICROINJECTIONS OF 2 GABA(B) RECEPTOR ANTAGONISTS

The cardiovascular effects of microinjections of two gamma-aminobutyri c acid (GABA) antagonists specifically acting on GABA(B) receptors, 2- hydroxy-saclofen (2-OH-S) and CGP-35348, into vasopressor sites of ros tral ventrolateral medulla (RVLM) were studied in rats anesthetized wi th urethan. Bilateral microinjection of 2-OH-S induced significant inc reases in mean arterial pressure (MAP) and heart rate (HR) in 21 of 26 RVLM vasopressor sites (81%); average increases obtained in the 26 si tes studied were +25.2 +/- 3.0 mmHg and +12.7 +/- 2.1 beats/min. Bilat eral microinjection of CGP-35348 induced significant increases in MAP and HR in 10 of 12 RVLM sites (83%). Average increases in the 12 sites studied were +27.6 +/- 3.9 mmHg and +14.6 +/- 2.5 beats/min. Sixteen rats received unilateral electrolytic lesions of one RVLM. Microinject ions of either 2-OH-S or CGP-35348 into vasopressor sites within the i ntact RVLM significantly antagonized the depressor responses observed after injections of baclofen (20 pmol) into the same sites, whereas bo th GABA(B) antagonists did not affect the depressor response induced b y microinjection of muscimol (5 pmol). These results suggest a tonic i nhibitory mechanism within the RVLM mediated by GABA(B) receptors invo lved in central cardiovascular regulation.