Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model

Shogo Watanabe, Shota Kumazaki, Shusei Yamamoto, Ikumi Sato, Kazuya Kitamori, Mari Mori, Yukio Yamori, Satoshi Hirohata

Research output: Contribution to journalArticle

Abstract

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 (SHRSP5/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 SHRSP5/Dmcr rats. Wistar Kyoto and SHRSP5/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, Nω-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 SHRSP5/Dmcr rat model demonstrates that NASH significantly aggravates cardiovascular risk.

Original languageEnglish
JournalInternational Journal of Experimental Pathology
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Arteriosclerosis
Fatty Liver
Nitric Oxide Synthase
NG-Nitroarginine Methyl Ester
High Fat Diet
Heart Ventricles
Fibrosis
Stroke
Cholesterol
Lipids
Mesenteric Arteries
Coronary Occlusion
Inbred SHR Rats
Cardiac Myocytes
Drinking Water
Myocardial Ischemia
Arginine
Cardiovascular Diseases
Pathology
Liver

Keywords

  • atherosclerosis
  • endothelial function
  • myocardial ischaemia
  • non-alcoholic steatohepatitis
  • SHRSP5/Dmcr

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model. / Watanabe, Shogo; Kumazaki, Shota; Yamamoto, Shusei; Sato, Ikumi; Kitamori, Kazuya; Mori, Mari; Yamori, Yukio; Hirohata, Satoshi.

In: International Journal of Experimental Pathology, 01.01.2019.

Research output: Contribution to journalArticle

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