Augmenting Renal Lymphatic Density Prevents Angiotensin II-Induced Hypertension in Male and Female Mice.

Abstract

BACKGROUND\nRenal inflammation and immune cell infiltration are characteristic of several forms of hypertension. Our lab has previously demonstrated that renal inflammation-associated lymphangiogenesis occurs in salt-sensitive and nitric oxide inhibition-induced hypertension. Moreover, enhancing renal lymphatic density prevented the development of these two forms of hypertension. Here, we investigated the effects of angiotensin II-induced hypertension on renal lymphatic vessel density in male and female mice.\n\n\nMETHODS\nand results: Male and female mice were infused with angiotensin II for two or three weeks. Compared to vehicle controls, angiotensin II-infused male and female mice had significantly increased renal lymphatic vessel density in association with pro-inflammatory immune cells in the kidneys of these mice. Direct treatment of lymphatic endothelial cells with angiotensin II had no effect since they lack angiotensin II receptors, however angiotensin II treatment of isolated splenocytes and peritoneal CD11b+ cells induced secretion of the lymphangiogenic growth factor VEGF-C in vitro. Utilizing our genetic mouse model of inducible renal lymphangiogenesis, we demonstrated that greatly augmenting renal lymphatic density prior to angiotensin II infusion prevented the development of hypertension in male and female mice and this was associated with a reduction in renal CD11c+F4/80- monocytes.\n\n\nCONCLUSION\nRenal lymphatics play a significant role in renal immune cell trafficking and blood pressure regulation, and represent a novel avenue of therapy for hypertension.