Role of γ-Aminobutyric Acid B Receptors in Baroreceptor Reflexes in Hypertensive Rats

Abstract

Abstract Previous studies demonstrated that stimulation of γ-aminobutyric acid B (GABA B ) receptors in the nucleus tractus solitarius of spontaneously hypertensive rats (SHR) elicited a larger increase in arterial pressure compared with control Wistar-Kyoto rats. Since stimulation of GABA B receptors in the nucleus tractus solitarius attenuates cardiovascular responses evoked by electrical stimulation of the aortic depressor nerve in normotensive rats and there is evidence of a central neural attenuation of aortic depressor nerve–evoked responses in SHR, we conducted studies to test the hypothesis that enhanced stimulation of GABA B receptors in the nucleus tractus solitarius in SHR is responsible 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 splanchnic sympathetic nerve activity in urethane-anesthetized control rats. These responses were not significantly altered by injection of the GABA B receptor antagonist CGP 35348 into the ipsilateral nucleus tractus solitarius. The responses evoked by aortic depressor nerve stimulation were attenuated in SHR. This attenuation was particularly apparent with more prolonged periods (>15 seconds) of high-frequency (25-Hz) stimulation, with the depressor and sympathetic nerve responses diminishing during the course of stimulation. This time- and frequency-dependent attenuation of baroreceptor-evoked depressor responses was reversed by injection of CGP 35348 into the ipsilateral nucleus tractus solitarius. Rats made hypertensive by treatment with deoxycorticosterone plus salt did not have attenuated aortic depressor nerve–evoked responses. These results suggest that alterations in GABA B -mediated neural transmission in the nucleus tractus solitarius contribute to the attenuation of the baroreceptor reflex observed in SHR.