Activation of GABA(A) but not GABA(B) receptors in the NTS blocked bradycardia of chemoreflex in awake rats

In the present study we analyzed effects of bilateral microinjections of mu scimol (a GABAA agonist) and baclofen (a GABAB agonist) into the nucleus tr actus solitarius (NTS) on bradycardic and presser responses to chemoreflex activation (potassium cyanide, 40 mu g/rat iv) in awake rats. Bilateral mic roinjections of muscimol (25 and 50 pmol/50 nl) into the NTS increased base line mean arterial pressure (MAP): 119 +/- 8 vs. 107 +/- 2 mmHg (n = 6) and 121 +/- 8 vs. 103 +/- 3 mmHg (n = 6), respectively. Muscimol at 25 pmol/50 nl reduced the bradycardic response to chemoreflex activation 5 min after microinjection; with 50 pmol/50 nl the bradycardic response to chemoreflex activation was reduced 5, 15, 30, and 60 min after microinjection. Neither muscimol dose produced an effect on the presser response of the chemoreflex . Effects of muscimol (50 pmol/50 nl) on basal MAP and on the bradycardic r esponse of the chemoreflex were prevented by prior microinjection of bicucu lline (a GABA(A) antagonist, 40 pmol/50 nl) into the NTS. Bilateral microin jections of baclofen (12.5 and 25 pmol/50 nl) into the NTS produced an incr ease in baseline MAP [137 +/- 9 vs. 108 +/- 4 (n = 7) and 145 +/- 5 vs. 105 +/- 2 mmHg (n = 7), respectively], no changes in basal heart rate, and no effects on the bradycardic response; 25 pmol/50 nl only attenuated the pres ser response to chemoreflex activation. The data show that activation of GA BAA receptors in the NTS produces a significant reduction in the bradycardi c response, whereas activation of GABAB receptors produces a significant re duction in the presser response of the chemoreflex. We conclude that 1) GAB AA but not GABAB plays an inhibitory role in neurons of the lateral commiss ural NTS involved in the parasympathetic component of the chemoreflex and 2 ) attenuation of the presser response of the chemoreflex by activation of G ABAB receptors may be due to inhibition of sympathoexcitatory neurons in th e NTS or may be secondary to the large increase in baseline MAP produced by baclofen.