Sesamin ameliorates arterial dysfunction in spontaneously hypertensive rats via downregulation of NADPH oxidase subunits and upregulation of eNOS expression

Acta Pharmacol Sin. 2013 Jul;34(7):912-20. doi: 10.1038/aps.2013.1. Epub 2013 Apr 29.

Abstract

Aim: Sesamin is one of the major lignans in sesame seeds with antihyperlipidemic, antioxidative and antihypertensive activities. The aim of this study was to examine the effects of sesamin on arterial function in spontaneously hypertensive rats (SHRs).

Methods: SHRs were orally administered sesamin (40, 80 and 160 mg·kg(-1)·d(-1)) for 16 weeks. After the rats were killed, thoracic aortas were dissected out. The vasorelaxation responses of aortic rings to ACh and nitroprusside were measured. The expression of eNOS and NADPH oxidase subunits p47(phox) and p22(phox) in aortas were detected using Western blotting and immunohistochemistry. Aortic nitrotyrosine was measured with ELISA. The total antioxidant capacity (T-AOC) and MDA levels in aortas were also determined.

Results: The aortic rings of SHRs showed significantly smaller ACh-induced and nitroprusside-induced relaxation than those of control rats. Treatment of SHRs with sesamin increased both the endothelium-dependent and endothelium-independent relaxation of aortic rings in a dose-dependent manner. In aortas of SHRs, the level of T-AOC and the expression of nitrotyrosine, p22(phox) and p47(phox) proteins were markedly increased, while the level of MDA and the expression of eNOS protein were significantly decreased. Treatment of SHRs with sesamin dose-dependently reversed these biochemical and molecular abnormalities in aortas.

Conclusion: Long-term treatment with sesamin improves arterial function in SHR through the upregulation of eNOS expression and downregulation of p22(phox) and p47(phox) expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / enzymology
  • Aorta, Thoracic / physiopathology*
  • Dioxoles / pharmacology*
  • Dioxoles / therapeutic use
  • Down-Regulation / drug effects
  • Down-Regulation / genetics*
  • Hypertension / drug therapy
  • Hypertension / enzymology
  • Hypertension / physiopathology
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Male
  • NADPH Oxidases / antagonists & inhibitors*
  • NADPH Oxidases / biosynthesis
  • Nitric Oxide Synthase Type III / biosynthesis*
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / physiology
  • Organ Culture Techniques
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / biosynthesis
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Up-Regulation / drug effects
  • Up-Regulation / genetics*

Substances

  • Dioxoles
  • Lignans
  • Protein Subunits
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • NADPH Oxidases
  • Cyba protein, rat
  • neutrophil cytosolic factor 1
  • sesamin