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-aminobutyric acid (GABA) antagonists specifically acting on GABA(B) receptors, 2-hydroxy-saclofen (2-OH-S) and CGP-35348, into vasopressor sites of rostral ventrolateral medulla (RVLM) were studied in rats anesthetized with urethan. Bilateral microinjection of 2-OH-S induced significant increases in mean arterial pressure (MAP) and heart rate (HR) in 21 of 26 RVLM vasopressor sites (81%); average increases obtained in the 26 sites studied were +25.2 +/- 3.0 mmHg and +12.7 +/- 2.1 beats/min. Bilateral 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. Microinjections of either 2-OH-S or CGP-35348 into vasopressor sites within the intact RVLM significantly antagonized the depressor responses observed after injections of baclofen (20 pmol) into the same sites, whereas both GABA(B) antagonists did not affect the depressor response induced by microinjection of muscimol (5 pmol). These results suggest a tonic inhibitory mechanism within the RVLM mediated by GABA(B) receptors involved in central cardiovascular regulation.