title: Antihypertensive therapy improves insulin resistance and serum levels of interleukin-6 and -10 in spontaneously hypertensive rats with steatohepatitis.
abstract: Metabolic syndrome based on insulin resistance (IR) and hypertension is a risk factor for advanced liver disease and cardiovascular disease in patients with nonalcoholic steatohepatitis (NASH). The present study investigated the effects of severe hypertension induced by a high‑salt (HS) diet and antihypertensive therapy on the pathophysiological condition of spontaneously hypertensive rats (SHRs) with steatohepatitis. Steatohepatitis was induced using a choline-deficient, L-amino acid-defined diet (CDAA). Male SHRs (7‑week‑old) were randomly divided into five groups: Those receiving 6 weeks of standard chow with a normal salt concentration, followed by an additional 8 weeks of standard chow or CDAA with a normal salt concentration (control and CDAA groups, respectively); and those receiving 6 weeks of standard chow with HS, followed by CDAA with HS for an additional 8 weeks, with or without the antihypertensive agents, amlodipine (Aml) or hydralazine. In the CDAA and CDAA+HS groups, blood pressure was significantly correlated with serum levels of insulin, fasting blood glucose and homeostasis model assessment (HOMA)‑IR. Antihypertensive therapy ameliorated the elevated glucose, insulin and HOMA‑IR. Furthermore, the increased levels of serum interleukin (IL)‑6 following the CDAA+HS diet were attenuated by antihypertensive therapy. The serum levels of IL‑10 were increased by antihypertensive therapy, and the decrease in the proportion of splenic CD4+CD25+forkhead box P3+ T cells observed following the CDAA+HS diet tended to be restored by Aml. In conclusion, antihypertensive therapy improved glucose metabolism and imbalances in cytokine expression in the rat model of hypertension with steatohepatitis, suggesting that antihypertensive therapy acting through immunological factors may be beneficial for patients with metabolic syndrome-associated NASH.
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Masaya
authors: M
authors: Kozono
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Hirofumi
authors: H
authors: Uto
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Rie
authors: R
authors: Ibusuki
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Shiho
authors: S
authors: Arima
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Kohei
authors: K
authors: Oda
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Hiroki
authors: H
authors: Taguchi
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Fumisato
authors: F
authors: Sasaki
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Yuichiro
authors: Y
authors: Nasu
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Shinichi
authors: S
authors: Hashimoto
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Hitoshi
authors: H
authors: Setoyama
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Shuji
authors: S
authors: Kanmura
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Masatsugu
authors: M
authors: Numata
authors: Department of HGF Tissue Repair and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Hirohito
authors: H
authors: Tsubouchi
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan.
authors: Akio
authors: A
authors: Ido
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015415:Biomarkers; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000959:Antihypertensive Agents; D015415:Biomarkers; D001786:Blood Glucose; D018932:Chemokine CCL2; D007328:Insulin; D016753:Interleukin-10; D015850:Interleukin-6; C067980:CD68 antigen, human; D000097382:CD68 Molecule