Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock

Autor: Solène Collin, Mathilde Renou de La Bourdonnaye, Chantal Montemont, Ferhat Meziani, Patrick Lacolley, Bruno Levy, Nacira Sennoun, Pierre Asfar, Anne-Gaëlle Dron
Přispěvatelé: Univ Angers, Okina, Université Henri Poincaré - Nancy 1 (UHP), Biologie Neurovasculaire Intégrée (BNVI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Risque cardiovasculaire, rigidité-fibrose et hypercoagulabilité (RCV), Université Henri Poincaré - Nancy 1 (UHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Geometry and Lighting (ALICE), INRIA Lorraine, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP)
Rok vydání: 2010
Předmět:
Male
Potassium
[SDV]Life Sciences [q-bio]
030204 cardiovascular system & hematology
Critical Care and Intensive Care Medicine
Intensive / Critical Care Medicine
Pediatrics
Polymerase Chain Reaction
Muscle
Smooth
Vascular
chemistry.chemical_compound
Phenylephrine
0302 clinical medicine
KATP Channels
Anesthesiology
inhibitors
Medicine
Mesenteric arteries
0303 health sciences
Shock
Septic
Potassium channel
Cell biology
Mesenteric Arteries
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Biochemistry
Shock (circulatory)
Emergency Medicine
France
medicine.symptom
Pneumology/Respiratory System
Blotting
Western
chemistry.chemical_element
Nitric Oxide
Nitric oxide
Pain Medicine
Potassium channels
03 medical and health sciences
Intensive care
medicine.artery
Animals
Rats
Wistar
030304 developmental biology
Aorta
Cardiovascular failure
business.industry
Septic shock
medicine.disease
Rats
chemistry
septic shock
business
Zdroj: Intensive Care Medicine
Intensive Care Medicine, 2011, 37 (5), pp.861-869. ⟨10.1007/s00134-011-2169-5⟩
Intensive Care Medicine, Springer Verlag, 2011, 37 (5), pp.861-869. ⟨10.1007/s00134-011-2169-5⟩
ISSN: 1432-1238
0342-4642
Popis: International audience; Purpose To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Methods Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. Results Arterial pressure as well as in vivo and ex vivo vascular reactivity were reduced by sepsis and improved by PNU-37883A but not by IbTX. Sepsis was associated with an up-regulation of mRNA and protein expression of vascular KATP channels, while expression of vascular BKCa channels remained unchanged. Selective iNOS inhibition blunted the sepsis-induced increase in aortic NO, decreased NF-κB activation, and down-regulated vascular KATP channel expression. Conclusions Vascular KATP but not BKCa channels are activated, over-expressed, and partially regulated by NO via NF-κB activation during septic shock. Their selective inhibition restores arterial pressure and vascular reactivity and decreases lactate concentration. The present data suggest that selective vascular KATP channel inhibitors offer potential therapeutic perspectives for septic shock.
Databáze: OpenAIRE
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