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Non‐alcoholic steatohepatitis aggravates nitric oxide synthase inhibition‐induced arteriosclerosis in SHRSP 5/Dmcr rat model
Author(s) -
Watanabe Shogo,
Kumazaki Shota,
Yamamoto Shusei,
Sato Ikumi,
Kitamori Kazuya,
Mori Mari,
Yamori Yukio,
Hirohata Satoshi
Publication year - 2018
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12301
Subject(s) - medicine , steatohepatitis , endothelial dysfunction , arteriosclerosis , endocrinology , ventricle , nitric oxide synthase , fibrosis , cardiology , fatty liver , nitric oxide , disease
Summary Non‐alcoholic steatohepatitis ( NASH ) is linked to increased cardiovascular risk, independent of the broad spectrum of metabolic syndrome risk factors. Stroke‐prone ( SP ) spontaneously hypertensive rats ( SHRSP 5/Dmcr) fed a high‐fat and high‐cholesterol ( HFC ) diet developed hepatic lesions similar to those in human NASH pathology. These rats simultaneously developed lipid deposits in the mesenteric arteries, cardiac fibrosis, endothelial dysfunction and left ventricle ( LV ) diastolic dysfunction. However, the intermediary factors between NASH and cardiovascular disease are still unknown. We investigated whether NASH aggravates nitric oxide ( NO ) synthase inhibition‐induced arteriosclerosis in SHRSP 5/Dmcr rats. Wistar Kyoto and SHRSP 5/Dmcr rats were divided into 4 groups of 5 and fed the stroke‐prone ( SP ) or HFC diets for 8 weeks. To induce NO synthase inhibition, N ω ‐nitro‐L‐arginine methyl ester hydrochloride (L‐ NAME ) mixed with drinking water was administered in the final 2 weeks. The NASH +L‐ NAME group demonstrated the following characteristics related to arteriosclerosis and myocardial ischaemia: (a) LV systolic dysfunction with asynergy, (b) replacement fibrosis caused by the shedding of cardiomyocytes and (c) arterial lipid deposition and coronary occlusion secondary to endothelial dysfunction. These characteristics were not observed in the NASH or non‐ NASH +L‐ NAME groups. The SHRSP 5/Dmcr rat model demonstrates that NASH significantly aggravates cardiovascular risk.