Alteration of endothelial CaMKII in AngII‐induced hypertensive mice

Abstract

Endothelial dysfunction found in AngII‐induced hypertension is characterized by an alteration of the delicate balance between reactive oxygen species (ROS) and nitric oxide (NO). Loss of endothelial Ca2+ homeostasis has also been shown in hypertension. Recent evidences suggest that CaMKII is activated by Ca2+ pulsars, a localized spontaneous Ca2+ signal and is involved in endothelial function. Since CaMKII is also sensitive to intracellular ROS, endothelial CaMKII and Ca2+ pulsars in an AngII‐induced hypertension mouse model was studied. Real‐time confocal imaging showed that acute exposure to AngII stimulated both Ca2+ pulsars and production of ROS. As expected, an increase in endothelial ROS production was found with dihydroethidium (DHE) in the AngII hypertensive compared to normotensive mice. Moreover, AngII‐induced hypertension appears to recruit activated CaMKII (T286) at the myoendothelial projection (MEP), sites of Ca2+ pulsars. Consistently, clustering of all endothelial CaMKII isoforms (α, β and δ) within the MEP has showed a similar distribution. Our data suggest that CaMKII activity is modulated by an increased ROS production and Ca2+ pulsars stimulation in AngII‐induced hypertensive mice. Supported by CIHR, FRQS, CFI and HSFC.