Enhancing Renal Lymphatic Expansion Prevents Hypertension in Mice

Catalina A Lopez Gelston; Dakshnapriya Balasubbramanian; Gabriella R Abouelkheir; Alexandra H Lopez; Kayla R Hudson; Eric R Johnson; Mariappan Muthuchamy; Brett M Mitchell; Joseph M Rutkowski

doi:10.1161/CIRCRESAHA.118.312765

Enhancing Renal Lymphatic Expansion Prevents Hypertension in Mice

Circ Res. 2018 Apr 13;122(8):1094-1101. doi: 10.1161/CIRCRESAHA.118.312765. Epub 2018 Feb 23.

Authors

Catalina A Lopez Gelston¹, Dakshnapriya Balasubbramanian¹, Gabriella R Abouelkheir¹, Alexandra H Lopez¹, Kayla R Hudson¹, Eric R Johnson¹, Mariappan Muthuchamy¹, Brett M Mitchell², Joseph M Rutkowski¹

Affiliations

¹ From the Department of Medical Physiology, Texas A&M College of Medicine, College Station.
² From the Department of Medical Physiology, Texas A&M College of Medicine, College Station. bmitchell@tamhsc.edu rutkowski@tamhsc.edu.

PMID: 29475981
DOI: 10.1161/CIRCRESAHA.118.312765

Abstract

Rationale: Hypertension is associated with renal infiltration of activated immune cells; however, the role of renal lymphatics and immune cell exfiltration is unknown.

Objective: We tested the hypotheses that increased renal lymphatic density is associated with 2 different forms of hypertension in mice and that further augmenting renal lymphatic vessel expansion prevents hypertension by reducing renal immune cell accumulation.

Methods and results: Mice with salt-sensitive hypertension or nitric oxide synthase inhibition-induced hypertension exhibited significant increases in renal lymphatic vessel density and immune cell infiltration associated with inflammation. Genetic induction of enhanced lymphangiogenesis only in the kidney, however, reduced renal immune cell accumulation and prevented hypertension.

Conclusions: These data demonstrate that renal lymphatics play a key role in immune cell trafficking in the kidney and blood pressure regulation in hypertension.

Keywords: blood pressure; hypertension; immune system; immunity; kidney; vascular endothelial growth factor C; vascular endothelial growth factor receptor-3.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Differentiation / biosynthesis
Antigens, Differentiation / genetics
Calcium-Binding Proteins
Cell Movement
Homeodomain Proteins / biosynthesis
Homeodomain Proteins / genetics
Hypertension / chemically induced
Hypertension / physiopathology
Hypertension / prevention & control*
Kidney / immunology*
Kidney / physiopathology
Lymphangiogenesis* / genetics
Lymphatic Vessels / physiopathology*
Macrophages / immunology
Mice
Mice, Transgenic
NG-Nitroarginine Methyl Ester / toxicity
Nitric Oxide Synthase Type III / antagonists & inhibitors
Organ Specificity
Receptors, G-Protein-Coupled / metabolism
Sodium Chloride, Dietary / toxicity
T-Box Domain Proteins / biosynthesis
T-Box Domain Proteins / genetics
Th1 Cells / immunology
Tumor Suppressor Proteins / biosynthesis
Tumor Suppressor Proteins / genetics
Vascular Endothelial Growth Factor D / biosynthesis
Vascular Endothelial Growth Factor D / genetics
Vascular Endothelial Growth Factor Receptor-3 / biosynthesis
Vascular Endothelial Growth Factor Receptor-3 / genetics

Substances

Adgre1 protein, mouse
Antigens, Differentiation
Calcium-Binding Proteins
Homeodomain Proteins
Receptors, G-Protein-Coupled
Sodium Chloride, Dietary
T-Box Domain Proteins
T-box transcription factor TBX21
Tumor Suppressor Proteins
Vascular Endothelial Growth Factor D
Vegfd protein, mouse
monocyte-macrophage differentiation antigen
prospero-related homeobox 1 protein
Nitric Oxide Synthase Type III
Nos3 protein, mouse
Vascular Endothelial Growth Factor Receptor-3
NG-Nitroarginine Methyl Ester