Oxidative stress induces gastric submucosal arteriolar dysfunction in the elderly

Abstract

Aim: To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.

Methods: Twenty male patients undergoing subtotal gastrectomy were enrolled in this study. Young and elderly patient groups aged 25-40 years and 60-85 years, respectively, were included. Inclusion criteria were: no clinical evidence of cardiovascular, renal or diabetic diseases. Conventional clinical examinations were carried out. After surgery, gastric submucosal arteries were immediately dissected free of fat and connective tissue. Vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured by isolated vascular perfusion. Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin (HE) staining and Verhoeff van Gieson (EVG) staining. The expression of xanthine oxidase (XO) and manganese-superoxide dismutase (Mn-SOD) was assessed by Western blotting analysis. The malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) content and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined according to commercial kits.

Results: The overall structure of vessel walls was shown by HE and EVG staining, respectively. Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients; however, cell layer number in the vessel wall increased significantly in the elderly group. Compared with submucosal arteries in young patients, the amount of vascular collagen fibers, lumen diameter and media cross-sectional area were significantly increased in elderly patients. Ach- and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients. Compared with the young group, the expression of XO and the contents of MDA and H₂O₂ in gastric submucosal arterioles were increased in the elderly group. In addition, the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group.

Conclusion: Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process.

Keywords: Aging; Gastric blood flow; Human; Oxidative stress; Vascular dysfunction.

Figure 1

Changes in vascular structure of gastric submucosal arteries isolated from young and elderly patients shown by hematoxylin and eosin and Verhoeff van Gieson staining. A: Young, hematoxylin and eosin (HE); B: Elderly, HE; C: Young, Verhoeff van Gieson (EVG); D: Elderly, EVG. Images were obtained at × 400, Bar 50 μm.

Figure 2

Effects of age on relaxant response to acetylcholine (A) and sodium nitroprusside (B) in gastric arterioles from young and elderly patients. Data are mean ± SE, n = 6. ^aP < 0.05 vs young group. Ach: Acetylcholine; SNP: Sodium nitroprusside.

Figure 3

Changes in malondialdehyde (A) and hydrogen peroxide (B) and the activities of superoxide dismutase (C) and glutathione peroxidase (D) in gastric submucosal arteries isolated from young and elderly patients. Data are mean ± SE, n = 10. ^aP < 0.05 vs young group. MDA: Malondialdehyde; H₂O₂: Hydrogen peroxide; SOD: Superoxide dismutase; GSH-Px: Glutathione peroxidase.

Figure 4

Expression of xanthine oxidase (A) and manganese-superoxide dismutase (B) protein in gastric mucosa substratum arteries isolated from young and elderly patients. ^aP < 0.05 vs young group. β-actin was used to normalize loading variations (each bar represents the mean ± SE of 4 independent experiments). XO: Xanthine oxidase; Mn-SOD: Manganese-superoxide dismutase.