INVOLVEMENT OF BOTH GABA-A AND GABA-B RECEPTORS IN TONIC INHIBITORY CONTROL OF BLOOD-PRESSURE AT THE ROSTRAL VENTROLATERAL MEDULLA OF THE RAT

The rostral ventrolateral medulla (RVLM) contains vasopressor neurons which increase vasomotor tone. Endogenous GABA is suggested to be involved in mediation of the tonic inhibition of vasopressor neurons in the RVLM. To obtain more precise information about GABAergic mechanisms in the RVLM, we microinjected GABA agonists and antagonists unilaterally into the RVLM and examined their effects on blood pressure and heart rate. In addition, involvement of the other inhibitory amino acids glycine, beta-alanine and taurine in blood pressure regulation in the rat RVLM was also investigated. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. The GABA(A) agonist muscimol (3-30 pmol) and the GABA(B) agonist baclofen (10-100 pmol) microinjected into the RVLM produced a decrease in blood pressure. The GABA(A) antagonist bicuculline (300 pmol) abolished the depressor response to muscimol (10 pmol) but not to baclofen (30 pmol) whereas the GABA(B) antagonist 2-hydroxysaclofen (1 nmol) abolished the depressor response to baclofen (30 pmol) but not to muscimol (10 pmol). Either bicuculline or 2-hydroxysaclofen alone produced a pressor response. Both antagonists inhibited depressor responses to nipecotic acid (7.7 nmol) and GABA (0.3 nmol). Glycine (0.13-4.0 nmol), beta-alanine (0.11-3.4 nmol) and taurine (0.08 - 2.4 nmol) microinjected into the RVLM also produced decreases in blood pressure. The glycine antagonist strychnine (0.58 nmol) abolished the depressor response to glycine, beta-alanine and taurine but not to GABA. The taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide) (1.3 nmol) inhibited the depressor response to beta-alanine and taurine but not to glycine and GABA. These results show that in the rat RVLM there exist GABA(A) and GABA(B) receptors, and that endogenous GABA tonically stimulates both GABA(A) and GABA(B) receptors to decrease arterial pressure. It seems unlikely that glycine and taurine are involved in mediation of the tonic inhibition of vasopressor neurons in the rat RVLM.