Avaliação da participação dos canais KATP hipotalâmicos na atividade autonômica cardíaca

Abstract

ATP-sensitive potassium channels (KATP) are important membrane proteins that can couple cellular metabolism to neurosecretory and electrophysiological activity according to the site of occurrence. The presence of KATP in hypothalamic neurons has been related to glucosensitive mechanisms, once glucose is the main energetic source used by neurons. Hypothalamic paraventricular nucleus (PVN) controls many different physiological functions, including autonomic control of the most diverse organic systems, and among them, the cardiovascular system. Besides, it has been shown that PVN neurons express the KATP channel, and neuronal glucosensitivity has also been described in this nucleus. However, the participation of those channels in cardiovascular control has not been described so far. Therefore, we aimed to investigate if the central pharmacological manipulation of KATP channel could play a role in the modulation of the cardiac autonomic outflow. For this purpose, male Wistar rats (250-300g) were submitted to stereotaxic surgery for guide cannula placement into the third ventricle (1,8mm caudal to Bregma and 8,2mm below the skull). Seven days later, animals underwent a electrocardiogram (ECG) record, before and after the central microinjection of vehicle (Molecusol 5%), glibenclamide (5mM, a KATP channel blocker) or diazoxide (25µM, a KATP channel opener). Heart rate variability of the ECG was analyzed by Fast Fourier Transform and statistical analysis was performed by One-Way ANOVA test. All procedures were and approved by the Ethical Committee in research of UFRRJ protocol: 002190/2014. We found no statistical difference in the heart rate (Control: 296,9±16,84 bpm vs 321,3±12,95 bpm, respectively basal and experimental, n=10; glibenclamide: 339,3±10,26 bpm vs. 326,3±12,23 bpm, n=10; diazoxide: 310,8±16,68 bpm vs 312,2±10,75 bpm, n=12) or spectral variability components, among the evaluated groups [high frequency (Control: 37,27±3,79 n.u. vs 43,18±4,534 n.u., n=11; glibenclamide: 47,08±4,718 n.u. vs 40,92±3,771 n.u., n=13; diazoxide: 49,31±2,951 n.u. vs 46,62±4,110 n.u., n=13) or low frequency (Control: 62,73±3,79 n.u. vs 56,82±4,534 n.u., n=11; glibenclamide: 52,92±4,718 n.u. vs 59,08±3,771 n.u., n=13; diazoxide: 50,69±10,64 n.u. vs 53,38±4,11 n.u., n=13)]. Those data are in agreement to the field of knowledge, where in vivo central manipulation of KATP channels in basal condition failed to evoke changes in mean arterial pressure. Moreover, electrophysiological studies in PVN neurons suggest that mechanisms of glucosensitivity in those cells are independent of KATP activity. All those information lead us to suggest that central pharmacological manipulation of KATP channels in basal condition do not alter cardiac autonomic parameters.