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

Abstract :

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.

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https://hal.univ-angers.fr/hal-03268454
Contributeur : Okina Université d'Angers <>
Soumis le : mercredi 23 juin 2021 - 11:01:18
Dernière modification le : dimanche 22 août 2021 - 03:21:56

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Solène Collin, Nacira Sennoun, Anne-Gaëlle Dron, Mathilde de la Bourdonnaye, Chantal Montemont, et al.. Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock. Intensive Care Medicine, Springer Verlag, 2011, 37 (5), pp.861-869. ⟨10.1007/s00134-011-2169-5⟩. ⟨hal-03268454⟩

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