Assimetria e lateralização nas vias descendentes cardiovasculares oriundas do hipotálamo dorsomedial

Abstract

Stress exposure causes centrally mediated cardiovascular andneuroendocrine responses. However, the mechanisms underlying theinterindividual variability in the amplitude of these responses remain to be further investigated. Then, it is worth attempting efforts to investigate the central areas that organize these differential cardiovascular responses. Previous studies using disinhibition of unilateral dorsomedial hypothalamus (DMH) by nanoinjecting the GABAA antagonist, bicuculline methiodide (BMI), revealed asymmetry in the cardiac control by DMH (with right-sided predominance) andlateralization in the control of the renal sympathetic activity. Aiming to extend these previous data, we next evaluated anatomic and functional asymmetry in the descending cardiovascular pathways from DMH. There were three different focuses: i) Seeking to reveal whether the DMH asymmetry implicates in the cardiac performance, we observed that injection of BMI into right DMH provokes greater cardiac positive chronotropy and inotropy. Such inotropic responses were likely independent on chronotropy and afterload influences, likely known tomodify the cardiac contractility. It was also detected cardiac ectopic beats,again greatly numerous following right DMH activation; ii) Assuming that the removal of the Gabaergic tone acts over DMH by injecting BMI allows an excitatory input, our second aim was to assess the contribution of EAAreceptors (EAA) to the asymmetry and lateralization evoked from unilateralDMH. We also evaluated whether these responses would be mediated byperiaqueductal gray. In anesthetized animals, injection of NMDA into unilateral DMH or periaqueductal gray (PAG) caused lateralized renal sympathetic responses. However, the tachycardia evoked from right DMH was greater that left DMH or left and right PAG. Anatomic experiments unraveled a bidirectional pathway between DMH and PAG. In non-anesthetized rats, inhibition of EAA receptors attenuated the stress-evoked tachycardia, but EAA receptors in the right DMH seem to govern the full tachycardia caused by stress; iii) Neurons in Raphe Pallidus (RP) receive dense inputs from DMH and rule pre-sympatheticcardiac neurons. In this regard, we shall to investigate the contribution of RP neurons to the asymmetry in the cardiac responses evoked from unilateral DMH. Stimulation of RP neurons caused positive chronotropism and inotropism similar to that observed after stimulation of right DMH. Inhibition of RP abolished the differences in the cardiac responses evoked from right and left DMH. We conclude that the asymmetry in the cardiac control by DMH depends on the EAA receptors and on the recruitment of RP neurons. Furthermore, the lateralized responses evoked from unilateral DMH depend on a descending lateralized synapse between from DMH to PAG. Complimentary analyses are required to better elucidate the mechanisms involved in these asymmetric and lateralized responses.