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1 Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil; and 2 Institut National de la Santé et de la Recherche Médicale Unité 288, Centre Hospitalier Universitaire Pitié-Salpêtrière, 75634 Paris Cedex 13, France
In the present
study we analyzed effects of bilateral microinjections of muscimol (a
GABAA agonist) and baclofen (a
GABAB agonist) into the nucleus
tractus solitarius (NTS) on bradycardic and pressor responses to
chemoreflex activation (potassium cyanide, 40 µg/rat iv) in awake
rats. Bilateral microinjections of muscimol (25 and 50 pmol/50 nl) into
the NTS increased baseline 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 pressor
response of the chemoreflex. Effects of muscimol (50 pmol/50 nl) on
basal MAP and on the bradycardic response of the chemoreflex were
prevented by prior microinjection of bicuculline (a
GABAA antagonist, 40 pmol/50 nl)
into the NTS. Bilateral microinjections of baclofen (12.5 and 25 pmol/50 nl) into the NTS produced an increase 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 pressor response to
chemoreflex activation. The data show that activation of
GABAA receptors in the NTS
produces a significant reduction in the bradycardic response, whereas
activation of GABAB receptors
produces a significant reduction in the pressor response of the
chemoreflex. We conclude that 1)
GABAA but not GABAB plays an inhibitory role in
neurons of the lateral commissural NTS involved in the parasympathetic
component of the chemoreflex and 2)
attenuation of the pressor response of the chemoreflex by activation of
GABAB receptors may be due to
inhibition of sympathoexcitatory neurons in the NTS or may be secondary
to the large increase in baseline MAP produced by baclofen.
heart rate; autonomic nervous system; cardiovascular regulation; peripheral chemoreceptors; GABAergic receptors; muscimol; baclofen; bicuculline
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