Home General Physiology and Biophysics 2020 General Physiology and Biophysics Vol.39, No.2, 157–168, 2020

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Quarterly, 80 pp. per issue
Founded: 1982
ISSN  1338-4325 (online)

Published in English

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General Physiology and Biophysics Vol.39, No.2, 157–168, 2020

Title: Epac-mediated relaxation in murine basilar arteries depends on membrane permeability of cyclic nucleotide analogues and endothelial aging
Author: Johannes Welter, Gabriele Pfitzer, Olaf Grisk, Jürgen Hescheler, Lubomir T. Lubomirov
Abstract: Cerebral blood supply is finely tuned by regulatory mechanisms depending on vessel caliber the disruption of which contributes to the development of diseases such as vascular dementia, Alzheimer’s and Parkinson ‘s diseases. This study scopes whether cAMP-mimetic-ligands relax young and aged murine cerebral arteries, whether this relates to the activation of PKA or Epac signaling pathways and is changed with advanced age. The hormone Urocortin-1 relaxed submaximally contracted young and old basilar arteries with a similar pD2 and DMAX (~ –8.5 and ~ 90% in both groups). In permeabilized arteries, PKA activation by 6-Bnz-cAMP or Epac activation by 8-pCPT-2’-O-Me-cAMP also induced relaxation with pD2 of –6.3 vs. –5.8 in old for PKA-ligands, and –4.4 and –4.0 in old for Epac-ligands. Furthermore, aging significantly increased submaximal Ca2+-induced force. The effect of 8-pCPT-2’-O-Me-cAMP on intact arteries was attenuated by aging or nitric oxide synthase inhibition. No relaxing effect in both age-groups was observed after treatment with PKA-activator, Sp-6-Phe-cAMPS. In conclusion, our results suggest that in intact basilar arteries relaxation induced by cAMP-mimetics refers only to the activation of Epac and is impaired by smooth muscle and endothelial aging. The study presents an interesting option allowing therapeutic discrimination between both pathways, possibly for the exclusive activation of Epac in brain circulatory system.
Keywords: Vascular tone — Aging — Basilar artery — PKA- and Epac-ligands — cAMP-membrane permeability
Published online: 26-Mar-2020
Year: 2020, Volume: 67, Issue: 2 Page From: 157, Page To: 168
doi:10.4149/gpb_2019055


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