Affiliation:
1. Department of Drugs and Medicines, School of Pharmaceutical Sciences São Paulo State University (UNESP) Araraquara São Paulo Brazil
2. Department of Pharmacology and Systems Physiology University of Cincinnati Cincinnati Ohio USA
3. Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases Massachusetts General Hospital and Harvard Medical School Charlestown Massachusetts USA
4. Department of Pharmacology, School of Medicine of Ribeirão Preto University of São Paulo Ribeirão Preto São Paulo Brazil
Abstract
AbstractThe paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC‐mediated signalling in stress responses is unknown. Therefore, we investigated the role of sGC within the PVN in cardiovascular, autonomic, neuroendocrine, and local neuronal responses to acute restraint stress in rats. Bilateral microinjection of the selective sGC inhibitor ODQ (1 nmol/100 nl) into the PVN reduced both the increased arterial pressure and the drop in cutaneous tail temperature evoked by restraint stress, while the tachycardia was enhanced. Intra‐PVN injection of ODQ did not alter the number of Fos‐immunoreactive neurons in either the dorsal cap parvocellular (PaDC), ventromedial (PaV), medial parvocellular (PaMP), or lateral magnocelllular (PaLM) portions of the PVN following acute restraint stress. Local microinjection of ODQ into the PVN did not affect the restraint‐induced increases in plasma corticosterone concentration. Taken together, these findings suggest that sGC‐mediated signalling in the PVN plays a key role in acute stress‐induced pressor responses and sympathetically mediated cutaneous vasoconstriction, whereas the tachycardiac response is inhibited. Absence of an effect of ODQ on corticosterone and PVN neuronal activation in and the PaV and PaMP suggests that PVN sGC is not involved in restraint‐evoked hypothalamus‐pituitary‐adrenal (HPA) axis activation and further indicates that autonomic and neuroendocrine responses are dissociable at the level of the PVN.
Funder
Fundação de Amparo à Pesquisa do Estado de São Paulo
National Institutes of Health