Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity

• DOI: 10.1371/journal.pone.0186311
• Publication Date: 2017-10-23T18:02:24Z
• Authors: Shubha Murthy; Olha M. Koval; Juan M. Ramiro Diaz; Santosh Kumar; Daniel Nuno; Jason A. Scott; Chantal Allamargot; Linda J. Zhu; Kim Broadhurst; Velarchana Santhana; William J. Kutschke; Kaikobad Irani; Kathryn G. Lamping; Isabella M. Grumbach
• Keywords: 0303 health sciences; Nitric Oxide Synthase Type III; Science; Q; R; Nitric Oxide; Cell Line; 03 medical and health sciences; Medicine; Animals; Humans; Phosphorylation; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Research Article

The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine important in transducing intracellular Ca2+ signals. While vitro data regarding the role of CaMKII regulation endothelial nitric oxide synthase (eNOS) are contradictory, its function vivo remains unknown. Using two novel transgenic models to express inhibitor peptides selectively endothelium, we examined effect on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, activation was low aortic wall. Consistently, systolic diastolic pressure, heart rate plasma levels were unaltered by inhibition. Moreover, inhibition had no significant NO-dependent vasodilation. These results confirmed studies rings transduced with adenovirus expressing peptide. In cultured cells, bradykinin treatment produced anticipated rapid influx transient whereas blocked phosphorylation Ser-1179 dephosphorylation at Thr-497. Ca2+/CaM binding resultant production decreased under Our demonstrate that plays an bradykinin-driven vitro, but does not regulate vasorelaxation or pressure conditions.