Abstract

Salt-induced hypertension is associated with chronic interstitial inflammation and increases in activated inflammatory immune cells in the kidney. It is currently unknown if these renal immune cell changes result from high blood pressure or directly from high salt concentrations. Using a salt-sensitive hypertension (SSH) mouse model and hydralazine (HDZ), we hypothesized that some renal immune cells are affected by high blood pressure, and some will be affected by the high salt content without increased systemic pressure. Three groups of mice (n=5 in each) were generated and given L-NAME via drinking water for 2 weeks, with two groups receiving a high salt (4%) diet for 3 weeks after a 2-week washout, and one of these receiving HDZ (250 mg/L) via drinking water simultaneously during the high salt diet. Systolic blood pressure was significantly decreased in the SSH group treated with HDZ, dropping to 119±1 mmHg from 141±1 mmHg (p<0.001) in the untreated SSH group. Kidneys were immunophenotyped via flow cytometry, and had decreased M2 macrophages (SSH: -55%, p=0.012; SSH+HDZ: -58%, p=0.0096), increased Th17 cells (SSH: 60%, p=0.0015; SSH+HDZ: 47%, p=0.0086), and increased natural killer cells (SSH: 223%, p=0.013; SSH+HDZ: 276%, p=0.0031). In the SSH group only, Th1 cells increased 50% (p=0.047), Th2 cells increased 67% (p=0.035), dendritic cells increased 31% (p=0.025), and CD3+ T cells decreased -46% (p=0.0092). qPCR of collected kidney tissue revealed a three-fold increase in the macrophage/lymphatic marker Lyve1 (p=0.014) only in the SSH group. These results imply that SSH plays a significant role in shaping renal immune cell populations and renal inflammation. Specific renal immune cell subsets undergo changes due to both the high salt and high systemic pressure while others undergo changes only due to the high salt. Future studies will evaluate the therapeutic potential for targeting these immune cell populations and the effect it has on salt-induced hypertension.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call