Contribuição dos receptores de grelina dos neurônios pré-motores simpáticos do hipotálamo paraventricular para o controle da função cardiovascular
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2018-05-09
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Universidade Federal de Goiás
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on the balance of the excitatory and inhibitory synapses, such as gabaergic ones, is
responsible for cardiovascular system modulation. The effects of ghrelin, a 28-amino acids
peptide, are mediated by subtype 1a of the growth hormone secretagogue receptor (GHSR1a),
densely expressed in the sympathetic pre-motor neurons of PVH. Therefore, this work
investigated the effects of ghrelin on the control exercised by PVH on cardiovascular system
and its relationship with gabaergic activity. For this purpose, mean systemic arterial pressure
(PAM) in the femoral artery and pressure in the left cardiac ventricle (LVP) of Wistar rats
(250-300 g) were measured by catheterization. Treatment with 100 nL of 0.03 nM ghrelin
injected directly into PVH reduced PAM by 40 ± 12 mmHg and the maximum blood pressure in
the left cardiac ventricle (LVPmax) by 28 ± 12 mmHg, as well as its derivative as a function of
time (LVdP / dTmax), a measure of inotropism, which was reduced by 2051 ± 946 mmHg / s,
without causing statistically significant changes in cardiac chronotropism. In contrast, to
demonstrate that the effects of ghrelin were mediated by GHS-R1a, the inhibition of this
receptor with 100 nL of PF04628935 (0.06 nM) in PVH caused an increase in PAM of 8 ± 3
mmHg and of LVPmax by 29 ± 8 mmHg; in addition to stimulating inotropism, with LVdP /
dTmax being elevated at 1449 ± 467 mmHg / s, and chronotropism, with elevated heart rate
at 29 ± 12 bpm. Finally, the comparison of its effects with muscimol, a GABAA receptor
agonist, demonstrated that ghrelin potentiated the reduction in blood pressure induced by
that drug, reducing PAM by 19 ± 5 mmHg, without significantly altering the pressure in the
cardiac left ventricle and inotropism. Interestingly, ghrelin promoted na increase in heart rate
by 27 ± 12 bpm, after muscimol injection. The present study demonstrated that the ghrelin
axis - GHS-R1a in PVH contributes to cardiovascular control and related these effects to
interactions with the gabaergic system.
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SANTANA, J. S. Contribuição dos receptores de grelina dos neurônios pré-motores simpáticos do hipotálamo paraventricular para o controle da função cardiovascular. 2018. 92 f. Dissertação (Mestrado Ciências Fisiológicas) - Universidade Federal de Goiás, Goiânia, 2018.