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

Abstract

High-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.

Keywords: Dahl salt-resistant rat; Dahl salt-sensitive rat; Fructose; Hypertension; Th17 lymphocytes; Treg lymphocytes.