Dendritic Cell Specific Jak2 Expression plays a role in in Salt‐Sensitive Hypertension through an ENaC‐dependent Mechanism

Abstract

Salt‐sensitivity of blood pressure affects 50% of hypertensive and 25% of normotensive individuals and is an independent predictor of death due to cardiovascular disease. We recently found that gamma and alpha subunits of the epithelial sodium channel (ENaCαγ) on dendritic cells mediate NADPH oxidase‐dependent formation of immunogenic isolevuglandin (IsoLG)‐protein adducts leading to inflammation and salt‐sensitive hypertension. We hypothesized that Jak2 expression in dendritic cells regulates expression of ENaCγ and promotes salt‐sensitive hypertension. Mice lacking Jak2 in CD11c+ cells developed blunted hypertension (123.8±4.7) during the high salt feeding phase of the N‐Nitro‐L‐arginine methyl ester hydrochloride (LNAME)/high salt model of salt‐sensitive hypertension compared to their wildtype littermate controls (140.5±6.5). These mice also exhibited less infiltration of monocyte/macrophages in their kidneys and less volume retention (69.55±5.8) in response to high salt‐feeding when compared to the wildtype litter mate controls (57.89±9.5). We also found that deletion of Jak2 in dendritic cells reduced the salt‐induced expression of ENaCγ in CD11c+ cells. Following high salt feeding, mice lacking Jak2 in DCs exhibited less aortic infiltration of CD11c+ cells with less expression of CD86 and production of IsoLGs. These results indicate that dendritic cell Jak2 plays a role in salt‐sensitive hypertension through an ENaC‐dependent mechanism.Support or Funding InformationK01HL130497R01HL147818T32HL144446