Maintenance of normal blood pressure is dependent on IP3R1-mediated regulation of eNOS - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2016

Maintenance of normal blood pressure is dependent on IP3R1-mediated regulation of eNOS

Résumé

Endothelial cells (ECs) are critical mediators of blood pressure (BP) regulation, primarily via the generation and release of vasorelaxants, including nitric oxide (NO). NO is produced in ECs by endothelial NO synthase (eNOS), which is activated by both calcium (Ca(2+))-dependent and independent pathways. Here, we report that intracellular Ca(2+) release from the endoplasmic reticulum (ER) via inositol 1,4,5-trisphosphate receptor (IP3R) is required for Ca(2+)-dependent eNOS activation. EC-specific type 1 1,4,5-trisphosphate receptor knockout (IP3R1(-/-)) mice are hypertensive and display blunted vasodilation in response to acetylcholine (ACh). Moreover, eNOS activity is reduced in both isolated IP3R1-deficient murine ECs and human ECs following IP3R1 knockdown. IP3R1 is upstream of calcineurin, a Ca(2+)/calmodulin-activated serine/threonine protein phosphatase. We show here that the calcineurin/nuclear factor of activated T cells (NFAT) pathway is less active and eNOS levels are decreased in IP3R1-deficient ECs. Furthermore, the calcineurin inhibitor cyclosporin A, whose use has been associated with the development of hypertension, reduces eNOS activity and vasodilation following ACh stimulation. Our results demonstrate that IP3R1 plays a crucial role in the EC-mediated vasorelaxation and the maintenance of normal BP.
Fichier principal
Vignette du fichier
2016 Yuang et al., Maitenance of normal blood.pdf (43.02 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-01802425 , version 1 (29-03-2020)

Identifiants

Citer

Qi Yuan, Jingyi Yang, Gaetano Santulli, Steven Reiken, Anetta Wronska, et al.. Maintenance of normal blood pressure is dependent on IP3R1-mediated regulation of eNOS. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113 (30), pp.8532 - 8537. ⟨10.1073/pnas.1608859113⟩. ⟨hal-01802425⟩
120 Consultations
26 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More