Activated pathogenic Th17 lymphocytes induce hypertension following high-fructose intake in Dahl salt-sensitive but not Dahl salt-resistant rats.

Eunjo Lee,Namkyung Kim,Sang-Hyun Kim,Inkyeom Kim,Hanna Jung,Sangwon Yoon,Jinjoo Kang,Hae-Ahm Lee

doi:10.1242/dmm.044107

Abstract

ABSTRACTHigh-salt intake and high-fructose intake are risk factors for hypertension via oxidative stress and inflammation. T helper (Th)17 lymphocytes play an important role in the development of hypertension. Here, we tested the hypothesis that activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in Dahl salt-sensitive (SS) but not Dahl salt-resistant (SR) rats. Eight-week-old male SS and SR rats were offered 20% fructose solution or tap water only for 4 weeks. Systolic blood pressure was measured by the tail-cuff method. T lymphocyte [Th17 and T regulatory (Treg)] profiling was determined via flow cytometry. The expression of Th17-related (IL-17A, IL-17RA, IL-23R and RORγt) and Treg-related (IL-10, CD25, FOXP3 and TGFβ) factors were measured via ELISA or qRT-PCR. Th17 lymphocytes isolated from high-fructose-fed SS rats were intraperitoneally injected into recipient SS and SR rats, and recombinant IL-23 protein was subcutaneously injected into SS and SR rats to induce hypertension.High-fructose intake induced hypertension via the activation of pathogenic Th17 lymphocytes in SS but not SR rats. Injection of activated Th17 lymphocytes isolated from fructose-fed SS rats induced hypertension via increase of serum IL-17A only in recipient SS rats. In addition, injection of IL-23 induced hypertension via activation of pathogenic Th17 lymphocytes only in SS rats.Thus, activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in SS but not SR rats. These results indicate that immunologic tolerance plays an important role in protection against hypertension in SR rats.

Highlights

Hypertension is a major risk factor for stroke, cardiovascular disease and renal disease
Some cases of hypertension are a result of clear causes, such as renal problem, abnormal cardiac output, excessive adrenal aldosterone production, or genetic causes, more than 90% of cases do not have an identifiable etiology and are classified as “essential.” Essential hypertension often coexists with obesity, abnormal lipid metabolism, aging, and insulin resistance, and is often considered as part of a complicated metabolic phenotype (Carretero and Oparil, 2000)
To determine whether high fructose intake had an effect on blood pressure, we measured the systolic blood pressure (SBP) of the rats for four weeks

Summary

Introduction

Hypertension is a major risk factor for stroke, cardiovascular disease and renal disease. High-fructose corn syrup and sucrose are added to various food products, and fructosesweetened beverages are a major source of dietary fructose intake worldwide (Hannou et al, 2018). Dietary components that increase blood pressure have become a big issue and many research groups have recently started to pay attention to fructose intake (Taskinen et al, 2019). Fructose elevates the blood pressure through oxidative stress, which induces hemodynamic effects such as increased sympathetic nervous system activity, endothelial dysfunction, activation of the renin-angiotensinaldosterone system, and inflammation (Caliceti et al, 2017; Johnson et al, 2009). High fructose, but not high glucose, intake with high salt diet induces salt-sensitive hypertension through reduced sodium excretion, increased salt retention, and impaired renal nitric oxide excretion (Ares and Ortiz, 2015; Gordish et al, 2017)

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