Cardiovascular Effects of Endogenous GABA in the Nucleus Tractus Solitarius

ABSTRACT

BACKGROUND: The nucleus tractus solitarius (NTS), the region of the brain stem in which primary baroreceptor afferents teminate, is critically important in the normal regulation of arterial pressure (AP). In the NTS, excitatory amino acids such as L-glutamate serve as the main neurotransmitter in the regulation of AP. However, the function of GABA in the NTS has not been established. To test the function of GABA, we applied GABAergic agents to the NTS. METHODS: The experiments were conducted on adult male Sprague-Dawley rats weighing 300-500g. A cannula (PE-50 tubing filled with heparinized saline) was inserted into the femoral artery for recording of AP and heart rate(HR). Another cannula was inserted into the femoral vein for administration of nitroprusside or phenylephrine. After rats were placed on a sterotaxic instrument, the dorsal surface of the medulla was exposed, and with the aid of a surgical microscope, the NTS was visualized. Drug injections were made into the NTS using single- or three-barreled grass micropipettes pulled to an outer diameter of 80-100(micro)m and connected to a 1(micro)l Hamilton syringe. RESULTS: The follwing results were obtained in this experiment. Injection into the NTS of 10 or 20 nmol nipecitic acid, a selective inhibitor of GABA untake, produced an increase in AP. The pressor responses evoked by two doses of nipecotic acid were not significantly different. Injection of GABA(A) agonist, musciml(5 pmol in 80 nl artificial CSF) and GABA(B) agonist, baclofen (20 pmol in 80 nl) into the NTS of urethane-anesthetized rats prodused an increase in AP of 16.6+/-1.3 and 27.6+/-1.5 mmHg, respectively. Thus the pressor response to GABA(B) agonist was greater than to GABA(A) agonist. On the other hand, microinjection of GABA(A) antagonist, bicuculline and GABA(B) antagonist, phaclofen into the NTS decreased AP by approximately 13.4+/-1.0 and 20.9+/- mmHg, respectively. Thus injection of nipecotic acid into the NTS was greater in control group compared with the muscimiol or baclofen groups. The AP changes caused by i.v. injection of nitroprusside or phenylephrine were smallest in control group and greatest in the baclofen group. When calculated as baroreflex sensitivity, the change was greatest in control group and smallest in the baclofen group. CONCLUSION: From these results it was concluded that GABA in the NTS plays an important role in the regulation of AP, especially through GABA(B) receptors, and have an inhibitory effect on baroreceptor reflex.