ROLE OF GAMMA-AMINOBUTYRIC-ACID-B RECEPTORS IN BARORECEPTOR REFLEXES IN HYPERTENSIVE RATS

Previous studies demonstrated that stimulation of gamma-aminobutyric a cid B (GABA(B)) receptors in the nucleus tractus solitarius of spontan eously hypertensive rats (SHR) elicited a larger increase in arterial pressure compared with control Wistar-Kyoto rats. Since stimulation of GABAB receptors in the nucleus tractus solitarius attenuates cardiova scular responses evoked by electrical stimulation of the aortic depres sor nerve in normotensive rats and there is evidence of a central neur al attenuation of aortic depressor nerve-evoked responses in SHR, we c onducted studies to test the hypothesis that enhanced stimulation of G ABA(B) receptors in the nucleus tractus solitarius in SHR is responsib le for the attenuation of the aortic depressor nerve-evoked responses. Electrical stimulation of the left aortic depressor nerve resulted in frequency-dependent decreases in arterial pressure, heart rate, and s planchnic sympathetic nerve activity in urethane-anesthetized control rats. These responses were not significantly altered by injection of t he GABA(B) receptor antagonist CGP 35348 into the ipsilateral nucleus tractus solitarius. The responses evoked by aortic depressor nerve sti mulation were attenuated in SHR. This attenuation was particularly app arent with more prolonged periods (>15 seconds) of high-frequency (25- Hz) stimulation, with the depressor and sympathetic nerve responses di minishing during the course of stimulation. This time- and frequency-d ependent attenuation of baroreceptor-evoked depressor responses was re versed by injection of CGP 35348 into the ipsilateral nucleus tractus solitarius. Rats made hypertensive by treatment with deoxycorticostero ne plus salt did not have attenuated aortic depressor nerve-evoked res ponses. These results suggest that alterations in GABA(B)-mediated neu ral transmission in the nucleus tractus solitarius contribute to the a ttenuation of the baroreceptor reflex observed in SHR.