Abstract

PASTORELLO, Mariella et al. Papel de la adrenomedulina cerebelosa en la hipertensión arterial. AVFT [online]. 2007, vol.26, n.2, pp.98-104. ISSN 0798-0264.

Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) belong to CGRP superfamily. Both peptides have overlapping biological actions particularly in regard to their very potent vasodilator properties. AM and CGRP binding sites are widely expressed in the central nervous system, in areas such as the hypothalamus and the rat cerebelar cortex. Central administration of AM or CGRP induces diuresis, natriuresis and increases arterial blood pressure. The functional role of AM in the cerebellum in unknown. The aim of the present study was to establish the possible relationship between cerebellar AM and CGRP and the regulation of cardiovascular function. To do so, we investigated the distribution and levels of CGRP and AM receptor binding sites in the brain 16- weeks-old normotensive (WKY) and SHR rats, using ¹²⁵I-hCGRPα and ¹²⁵I-hAM_13-52 as radioligands. As previously reported, CGRP and AM receptor sites are discretely and differentially distributed in the rat cerebellum cortex, with a preponderance of AM binding sites. Levels of CGRP receptor sites are found to be slightly higher in SHR, and higher levels of AM binding sites are detected in the granular cell layer of the cerebellum of SHR. To establish the possible signaling pathway of AM in cerebellum, we assessed AM-induced nitric oxide synthase activity (NOS). AM increased NOS activity, and this effect was blocked by the selective AM receptor antagonist AM_22-56. The expression of ERK1/2 and p-ERK activated was determined in WKY and SHR rat cerebellum. We show that in SHR rats an increased expression of p-ERK when compared with WKY control rats. It thus appears that levels of CGRP and AM binding sites, and p-ERK 1/2 expression are differentially altered in cerebellum of SHR rats. Our data show for the first time a role for cerebellar AM in the cardiovascular regulation.

Keywords : adrenomedullin; hypertension; cerebellum; nitric oxide; MAPK.

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