Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system

Department of Pharmacological and Physiological Science, St. Louis University, St. Louis, Missouri Submitted 27 October 2008 ; accepted in final form 20 May 2009 Nesfatin-1 is a recently discovered hypothalamic peptide that was shown to suppress food intake through a melanocortin-3/4 receptor-dependent mechanism. Since nesfatin-1 mRNA is detected in the paraventricular nucleus of the hypothalamus, and because many peptides that alter food intake also influence cardiovascular function, we tested the ability of centrally administered nesfatin-1 to affect mean arterial pressure (MAP) in conscious, freely moving rats. Significant increases in MAP were observed following intracerebroventricular administration of nesfatin-1. Pretreatment with either the melanocortin-3/4 receptor antagonist, SHU9119 (intracerebroventricular), or the -adrenergic antagonist, phentolamine (intra-arterial), abrogated the rise in MAP induced by nesfatin-1, indicating that nesfatin-1 may interact with the central melanocortin system to increase sympathetic nerve activity and lead to an increase in MAP. Thus we have identified a novel action of nesfatin-1, in addition to its anorexigenic effects, to stimulate autonomic nervous system activity. autonomics; hypothalamus; appetite Address for reprint requests and other correspondence: G. L. C. Yosten, Saint Louis Univ., Dept. of Pharmacological and Physiological Science, 1402 S. Grand Blvd., St. Louis, MO 63104 (e-mail: gyosten{at}slu.edu )