INFLUENCE OF INTRRMITTENT HYPOXIC TRAINING ON HAEMODYNAMIC EFFECTS OF NNOS ACTIVATION IN MEDULLARY CARDIOVASCULAR NEURONS OF RATS
L.M. Shapoval, LS. Pobigailo, LG. Stepanenko, OV. Dmytrenko, VO. Bury, VF. Sagach.
О.О. Bogomoletz Institute of Physiology of National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz56.01.062
Abstract
In our experiments, male Wistar rats, body weight 300 g ± 40 g, were exposed to intermittent hypoxia in a special chamber by its ventilation with hypoxic mixture containing 12% O2 in N2 5 times a day for 15 minutes with 15 min break for 10 days. After completing intermittent hypoxic training, in acute experiments on anesthetized with urethane (1.7 g/kg) rats, we studied changes in the systemic arterial pressure (SAP) induced by a modulation of neuronal NO-synthase (nNOS) ac-tivity in the neurons of the medullary cardiovascular nuclei (nucleus of tractus solitarius, NTS; nucleus ambiguous, AMB, lateral reticular nucleus, LRN). In control rats housed in normoxic conditions, nNOS activation with injections of L-arginine (5.8 - 58.0 nmol) into the medullary nuclei involved in the cardiovascular control induced the SAP lowering in most experiments in a dose-dependent manner. In rats submitted to intermittent hypoxic training, nNOS activation with injections of L-arginine (5.8 - 58.0 nmol) into the medullary nuclei under study resulted in hypotensive responses which were more expressed as compared with those responses induced by its injections into the medullary nuclei in rats under normoxia. The data obtained give evidence for some additional activation of neuronal NO-synthase in the neurons of the medullary nuclei following intermittent hypoxic training. Effects of nNOS activation were comparable in all the tested nuclei. The effect of nNOS activation was quite short- lasting, it was the most pronounced on the first day after completing hypoxic training. In three days after hypoxic training, injections of L-arginine into tested medullary nuclei resulted in the SAP drop that was similar to that in control animals housed in normoxic conditions. On the contrary, inhibition of nNOS in the neurons induced by injections of NOS-1-antagonist L-NNA (23.0 nmol) into the medullary cardiovascular nuclei resulted in a comparable increase in the SAP in both control and hypoxically trained rats. Effects of L-arginine injections into the medullary nuclei were blocked by preliminary administration of a specific nNOS inhibitor 7-nitroindazol. We noticed that intermittent hypoxic training was followed with the SAP elevation observed on the first day after training. Although it was statistically insignificant, and we observed the elevated SAP just after completing hypoxic training, these data provide evidence to support the concept that rats submitted to intermittent hypoxia exhibit an increase in sympathetic activity. The SAP elevation might be also induced by the stressor effect of keeping rats in a chamber to provide hypoxic training. There is an impression that intermittent hypoxic training might lead to two simultaneous but opposite directed results: an activation of sympathetic nervous system and an activation of nNOS in the medullary neurons.
Keywords:
Intermittent hypoxic training, neuronal NO-syn-thase, medullary cardiovascular neurons.
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