Gamma-Aminobutyric acid (GABA) and the GABA antagonist bicuculline methiodide were used to investigate the role of GABAergic transmission in the rostral and caudal ventrolateral medulla in 12- to 13-wk-old spontaneously hypertensive (SH) (n = 7) and normotensive, control Wistar-Kyoto (WKY) (n = 7) rats. Animals were anesthetized with urethan (1.25 g/kg sc), paralyzed with gallamine triethiodide (10 mg/kg iv), and artificially ventilated. Femoral arterial and venous catheters were inserted for the measurement of mean arterial pressure (MAP) and heart rate responses and for intravenous infusions. The ventral surface of the brain stem then was exposed. The responsiveness of the rostral ventrolateral medulla to GABA was compared in SH and WKY rats using unilateral microinjections (30 nl) of GABA at 1, 10, and 100 mM concentrations, which produced significantly (P less than 0.05) larger decreases of MAP in SH rats compared with WKY at the 10 and 100 mM concentrations (-37.3 +/- 2.8 mmHg for SH vs. -27.3 +/- 2.7 mmHg for WKY at 100 mM). Tonic GABAergic inhibition was gauged using bilateral microinjections (30 nl) of bicuculline (2 and 4 mM) into the rostral ventrolateral medulla, which caused significantly larger increases in MAP in the WKY group (+84.8 +/- 8.5 mmHg at 4 mM) compared with the SH group (+14.9 +/- 5.8 mmHg at 4 mM). In contrast, the ability to drive sympathetic outflow by microinjection of L-glutamate in the rostral ventrolateral medulla was not significantly different between WKY and SH rats.(ABSTRACT TRUNCATED AT 250 WORDS)