Time restricted feeding decreases renal innate immune cells and blood pressure in hypertensive mice.

BACKGROUND: Renal innate immune cell accumulation and inflammation are associated with hypertension. Time restricted feeding (TRF) has been reported to decrease inflammation and blood pressure. Whether TRF can decrease blood pressure by decreasing renal innate immune cells in hypertension is unknown. METHODS AND RESULTS: We determined whether TRF can decrease blood pressure in two separate mouse models of hypertension, N(G)-nitro-L-arginine methyl ester hydrochloride-induced hypertension (LHTN) and salt-sensitive hypertension (SSHTN). Once hypertension was established after 2 days, TRF (12-h food/12-h no food) for 4 weeks significantly decreased systolic blood pressure in both LHTN and SSHTN mice despite no differences in the amount of food eaten or body weight between groups. Activated macrophages and dendritic cells in the kidneys of both LHTN and SSHTN mice were decreased significantly in mice that underwent TRF. This was associated with an improvement in kidney function (decreased serum creatinine, decreased fractional excretion of sodium, and increased creatinine clearance) which achieved significance in LHTN mice and trended towards improvement in SSHTN mice. CONCLUSIONS: Our findings demonstrate that TRF can significantly decrease renal innate immune cells and blood pressure in two mouse models of hypertension.

A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice.

Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatics regulate inflammation through clearance of immune cells and excess interstitial fluid. Previously, we demonstrated increasing renal lymphangiogenesis prevents hypertension in mice. We hypothesized that targeted nanoparticle delivery of vascular endothelial growth factor-C (VEGF-C) to the kidney would induce renal lymphangiogenesis, lowering blood pressure in hypertensive mice. A kidney-targeting nanoparticle was loaded with a VEGF receptor-3-specific form of VEGF-C and injected into mice with angiotensin II-induced hypertension or LNAME-induced hypertension every 3 days. Nanoparticle-treated mice exhibited increased renal lymphatic vessel density and width compared to hypertensive mice injected with VEGF-C alone. Nanoparticle-treated mice exhibited decreased systolic blood pressure, decreased pro-inflammatory renal immune cells, and increased urinary fractional excretion of sodium. Our findings demonstrate that pharmacologically expanding renal lymphatics decreases blood pressure and is associated with favorable alterations in renal immune cells and increased sodium excretion.