Cerebellar adrenomedullin: A new target for blood pressure regulation

摘要: Adrenomedullin (AM) and their receptor components, CRLR, RAMP1, RAMP2 RAMP3 are widely expressed in the central nervous system, including cerebellum. Recent evidence suggests a role for cerebellar adrenomedullinergic system blood pressure (BP) regulation. We assessed AM, RAMP2, CRLR expression; AM signaling pathway vermis of WKY SHR rats.  Our findings demonstrated that RAMP1 RAMP3  expression was higher cerebellum rats, while lower than those both 8 16 week old In regard pathways, we show activates ERK, increases cAMP production, cGMP production NO accumulation. These effects mediated through activation 1 receptor, since 22-52 blunted action, meanwhile increase is also stimulation AM2 CGRP receptors.  Furthermore, decreased TBARS antioxidant enzymes basal activity:  catalase (CAT), gluthation peroxidase (GPx) superoxide dismutase (SOD).   During hypertension, pathways altered.  Effectively, rats activity three unable to affect these pathways; AM-induced ERK1/2 smaller magnitude WKY; increased cGMP/NO stimulate this pathway.  We anticipated possible functional on BP Indeed, vivo microinjection into caused profound, dose dependent, hypotensive effect but not normotensive Co-injections putative antagonist, 22–52 abolished decreases MAP evoked by showing acts its AM1 reduce pressure.  demonstrate dysregulation during suggest plays an important regulation BP.  Likewise, they constitute novel mechanism control which has been described so far.