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

Autor:	Murthy S; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.; Iowa City Veterans Affairs Healthcare System, Iowa City, Iowa, United States of America., Koval OM; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.; Iowa City Veterans Affairs Healthcare System, Iowa City, Iowa, United States of America., Ramiro Diaz JM; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Kumar S; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Nuno D; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Scott JA; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Allamargot C; Central Microscopy Research Facility, Office of Vice President of Research and Economic Development, University of Iowa, Iowa City, Iowa, United States of America., Zhu LJ; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Broadhurst K; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Santhana V; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Kutschke WJ; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Irani K; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.; Iowa City Veterans Affairs Healthcare System, Iowa City, Iowa, United States of America., Lamping KG; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.; Iowa City Veterans Affairs Healthcare System, Iowa City, Iowa, United States of America.; Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America., Grumbach IM; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.; Iowa City Veterans Affairs Healthcare System, Iowa City, Iowa, United States of America.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2017 Oct 23; Vol. 12 (10), pp. e0186311. Date of Electronic Publication: 2017 Oct 23 (Print Publication: 2017).
DOI:	10.1371/journal.pone.0186311
Abstrakt:	The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS) are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO production in vitro were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation in vitro, but does not regulate NO production, vasorelaxation or blood pressure in vivo under baseline conditions.
Databáze:	MEDLINE
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