Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase

American Journal of Physiology. Heart and Circulatory Physiology
Daniela Dal-SeccoJamil Assreuy

Abstract

G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP). Heart function was assessed by isolated and perfused heart, echocardiography, and β-adrenergic receptor binding. GRK2 was determined by immunofluorescence and Western blot analysis in the heart and isolated cardiac myocytes. Sepsis increased NOS2 expression in the heart, increased plasma nitrite + nitrate levels, and reduced isoproterenol-induced isolated ventricle contraction, whole heart tension development, and β-adrenergic receptor density. Treatment with 1400W or with GRK2 inhibitor prevented CLP-induced cardiac hyporesponsiveness 12 and 24 h after CLP. Increased labeling of total and phosphorylated GRK2 was detected in hearts after CLP. With treatment of 1400W or in hearts taken from septic NOS2 knockout mice, the ...Continue Reading

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Citations

Jan 20, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Heddwen L Brooks, Merry L Lindsey
Jan 20, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Merry L LindseyMarielle Scherrer-Crosbie
Jul 22, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Merry L LindseyDouglas Curran-Everett
Jan 9, 2019·Frontiers in Physiology·Camila Iansen IrionLina A Shehadeh
Apr 9, 2019·The Journal of International Medical Research·Fei YangZhuang Chen
Jul 12, 2021·Autonomic Neuroscience : Basic & Clinical·Jacquie BakerSatish R Raj
Oct 9, 2021·Clinical Science·Thiele Osvaldt RosalesJamil Assreuy

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Methods Mentioned

BETA
equilibrium
fluorescence microscopy
confocal microscopy

Software Mentioned

Image Laboratory
ImageJ
Leica Qwin
GraphPad Prism
Plugins

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