• Neuroscience · Jun 2014

    Antihypertensive and neuroprotective effects of catestatin in spontaneously hypertensive rats: interaction with GABAergic transmission in amygdala and brainstem.

    • E Avolio, S K Mahata, E Mantuano, M Mele, R Alò, R M Facciolo, G Talani, and M Canonaco.
    • Comparative Neuroanatomy Laboratory of Biology, Ecology and Earth Science Dept. (DiBEST), University of Calabria, Ponte P. Bucci 4B, 87030 Arcavacata di Rende, Cosenza, Italy; VA San Diego Healthcare System/Department of Medicine, University of California-San Diego, La Jolla, CA 92093-0838, USA; Department of Pathology, University of California-San Diego, La Jolla, CA 92093-0838, USA. Electronic address: eavolio@ucsd.edu.
    • Neuroscience. 2014 Jun 13; 270: 485748-57.

    AbstractThe chromogranin A-derived peptide catestatin (CST) exerts sympathoexcitatory and hypertensive effects when microinjected into the rostral ventrolateral medulla (RVLM: excitatory output); it exhibits sympathoinhibitory and antihypertensive effects when microinjected into the caudal ventrolateral medulla (CVLM: inhibitory output) of vagotomized normotensive rats. Here, continuous infusion of CST into the central amygdalar nucleus (CeA) of spontaneously hypertensive rats (SHRs) for 15 days resulted in a marked decrease of blood pressure (BP) in 6-month- (by 37 mm Hg) and 9-month- (by 65 mm Hg)old rats. Whole-cell patch-clamp recordings on pyramidal CeA neurons revealed that CST increased both spontaneous inhibitory postsynaptic current (sIPSC) amplitude plus frequency, along with reductions of sIPSC rise time and decay time. Inhibition of GABAA receptors (GABAARs) by bicuculline completely abolished CST-induced sIPSC, corroborating that CST signals occur through this major neuroreceptor complex. Hypertension is a major risk factor for cerebrovascular diseases, leading to vascular dementia and neurodegeneration. We found a marked neurodegeneration in the amygdala and brainstem of 9-month-old SHRs, while CST and the GABAAR agonist Muscimol provided significant neuroprotection. Enhanced phosphorylation of Akt and ERK accounted for these neuroprotective effects through anti-inflammatory and anti-apoptotic activities. Overall our results point to CST exerting potent antihypertensive and neuroprotective effects plausibly via a GABAergic output, which constitute a novel therapeutic measure to correct defects in blood flow control in disorders such as stroke and Alzheimer's disease.Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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