Is treatment with Losartan able to prevent the increase in LC activity in rats exposed to cold?

• Grant number: 11/20025-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2011
• End date: November 30, 2012
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Janete Aparecida Anselmo Franci
• Grantee: Talita Assis de Moraes
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The existence of neurons that produce angiotensin II (Ang II) and distribution of receptors for several central areas show the organization of a brain system that has this peptide as an important substance modulating many functions controlled by the central nervous system, such as cardiovascular, the limbic system and areas involved with sensory and motor responses (Saavedra, 2005). Besides these functions, Ang II modulates the responses of organisms to stress. Angiotensin receptors are found in areas involved in the hypothalamic-pituitary-adrenal axis, as the PVN and median eminence, and when stimulated by Ang II increases the release of CRH and ACTH. Ang II increases the behavioral responses to stress, to activate higher brain centers. We recently demonstrated that cold stress for 4 or 8 weeks increases sympathetic activity and induces ovarian installation of Polycystic Ovary Syndrome (PCOS) in female rats. This effect was mediated by activation of neurons in the Locus Coeruleus (LC) since cold induced an increase of LC activity (assessed by Fos expression) and that lesion of these neurons prevented the installation of this pathology. It is an aim of this laboratory to assess whether the central or peripheral blockade of increased sympathetic activity induced by cold may prevent the installation of PCOS in this experimental model. The peripheral blockade of adrenergic receptors is currently being tested in our laboratory by oral administration of propranolol, a beta-adrenergic blocker. Since it is known that Ang II is secreted in response to stress, and that it stimulates the neurons of the LC (and thus should stimulate sympathetic activity), the objective of this work is to verify if an AT1 receptor blocker of Ang II (losartan) could block the increased activity of LC neurons induced by a single exposition to cold. Data from the present experiment should guide future experiments to evaluate the effectiveness of this blocker in preventing the installation of PCO induced by this type of stress. (AU)