Nesfatin‐1 acts through a central POMC‐CRH‐OT circuit to increase mean arterial pressure

Abstract

Nesfatin‐1, a recently discovered brain/gut peptide, was originally described to potently inhibit food intake through interaction with the central melanocortin system (CMS), the central oxytocin system (COTS), and neurons producing corticotrophin releasing hormone (CRH). We previously have shown that central injection of nesfatin‐1 led to an increase in mean arterial pressure (MAP) that was also dependent upon the presence of functional central melanocortin and oxytocin receptors, and hypothesized that the cardiovascular effect of nesfatin‐1 would be dependent upon CRH neurons as well. We therefore pretreated conscious male rats with the CRH receptor antagonist, astressin‐2B, before treatment with nesfatin‐1, and found that blockade of CRH receptors abolished the ability of nesfatin‐1 to increase MAP. Several lines of evidence suggest that COT and CRH systems can act as downstream effectors of the CMS; however, little evidence exists as to the order of activation of oxytocin and CRH systems in this circuit. Pretreatment with the OT receptor antagonist, OVT, prior to central administration of a pressor dose of CRH, abrogated the CRH‐induced increase in MAP. Thus we have gained insight not only into the mechanism of nesfatin's central hypertensive actions, but also the hierarchy of neural networks within the hypothalamus projecting to brainstem cardiovascular centers. Supported by NIH #HL66023.