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1 Physiol. & Biophysics, University of Sao Paulo, Sao Paulo, SP, Brazil
2 Physiol. & Biophysics, University of Sao Paulo, Sao Paulo, SP, Brazil; Department of Psychiatry , University of Cincinnati, Cincinnati, Ohio, United States
3 Physiol.& Biophysics, University of Sao Paulo, Brazil; Department of Psychiatry , University of Cincinnati, Cincinnati, Ohio, United States
4 Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio, United States
* To whom correspondence should be addressed. E-mail: javier.stern{at}uc.edu.
Activation of oxytocinergic (OT) projections from the hypothalamic paraventricular nucleus (PVN) to the nucleus of the tractus solitarii (NTS) contributes to cardiovascular adjustments during exercise training (EXT). Moreover, a deficit in this central OTergic pathway is associated with altered cardiovascular function in hypertension. Since PVN catecholaminergic inputs, known to be activated during EXT, modulate PVN cardiovascular related functions, we aimed here to determine whether remodeling of PVN (nor)adrenergic innervation occurs during EXT, and whether this phenomenon is affected by hypertension. Confocal immunofluorescence microscopy and tract tracing were used to quantify changes in (nor)adrenergic innervation density in PVN subnuclei and in identified dorsal vagal complex (DVC) projecting neurons (PVN-DVC) in EXT normotensive (WKY) and hypertensive (SHR) rats. In WKY, EXT increased the density of PVN dopamine
hydroxylase immunoreactivity (DBHir) (160%). Furthermore, the number and density of DBHir boutons overlapping PVN-DVC OTergic neurons was also increased during EXT (130%), effects that were blunted in SHR rats. Conversely, while DBHir in the medial parvocellular subnucleus (an area enriched in corticotropin-releasing hormone neurons) was not changed by EXT in WKY rats, a diminished DBHir was observed in SHR trained rats. Overall, these data support that the PVN (nor)adrenergic innervation undergoes plastic remodeling during EXT, an effect that is differentially affected during hypertension. The functional implications of PVN (nor)adrenergic remodeling in relation to the central peptidergic control of cardiovascular function during EXT are discussed.
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