1887
Volume 2019, Issue 3
  • ISSN: 0253-8253
  • EISSN: 2227-0426

Abstract

Peritoneal dialysis solution (PDS) dilates peritoneal microvessels predominantly by the activation of the endothelial nitric oxide (NO) pathway. We made an incidental observation of decreased PDS-induced, NO-dependent peritoneal microvascular vasoreactivity in elderly rats naïve to PDS exposure. We hypothesized that this subordinate NO-mediated peritoneal microvascular vasoreactivity is caused by increased oxidative stress in the aged endothelium, which compromises NO bioavailability in the elderly, and that peritoneal microvascular vasoreactivity can be improved by the supplementation of antioxidant glycine to PDS. We studied PDS-mediated vasoreactivity of four intestinal visceral arterioles of different orders by intravital microscopy in weaned, adult, and elderly rats to (i) confirm subordinate vasoreactivity to PDS in elderly rats; (ii) restore vasoreactivity by glycine supplementation; and (iii) establish age as an independent risk factor for endothelial cell dysfunction. In a crossover series, peritoneal microvascular vasoreactivity to PDS exposure was remarkably decreased in elderly rats. This subordinate vasoreactivity was completely restored by the supplementation of glycine to PDS. In a separate series, we assessed endothelial cell function in weaned and adult rats using the cumulative acetylcholine concentration–response curves. Unlike the adults, the weaned rats demonstrated remarkable sensitivity and reactivity to cumulative acetylcholine concentrations, suggesting the dependency of endothelial cell function on age. Aging is an independent risk factor for peritoneal microvascular endothelial cell dysfunction. Endothelial function in the elderly can be recovered by reinforcing the bioavailability of endothelial-derived NO through glycine. Dietary glycine supplementation is a potential therapeutic strategy to decrease the burden of oxidative stress on the aged endothelium.

Loading

Article metrics loading...

/content/journals/10.5339/qmj.2019.19
2019-12-24
2020-11-29
Loading full text...

Full text loading...

/deliver/fulltext/qmj/2019/3/qmj.2019.19.html?itemId=/content/journals/10.5339/qmj.2019.19&mimeType=html&fmt=ahah

References

  1. Zakaria ER, Patel AA, Li N, Matheson PJ, Garrison RN. Vasoactive components of dialysis solution. Perit Dial Int. 2008; 28:3:283295.
    [Google Scholar]
  2. Zakaria ER, Hunt CM, Li N, Harris PD, Garrison RN. Disparity in osmolarity-induced vascular reactivity. J Am Soc Nephrol. 2005; 16:10:29312940.
    [Google Scholar]
  3. Zakaria ER, Althani A, Fawzi AA, Fituri OM. Molecular mechanisms of peritoneal dialysis-induced microvascular vasodilation. Adv Perit Dial. 2014; 30::98109.
    [Google Scholar]
  4. Sandoo A, van Zanten JJ, Metsios GS, Carroll D, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J. 2010; 4::302312.
    [Google Scholar]
  5. Mistriotis P, Andreadis ST. Vascular aging: Molecular mechanisms and potential treatments for vascular rejuvenation. Ageing Res Rev. 2017; 37::94116.
    [Google Scholar]
  6. Bochenek ML, Schutz E, Schafer K. Endothelial cell senescence and thrombosis: Ageing clots. Thromb Res. 2016; 147::3645.
    [Google Scholar]
  7. Prattichizzo F, Bonafe M, Ceka A, Giuliani A, Rippo MR, Re M, et al.  Endothelial Cell Senescence and Inflammaging: MicroRNAs as Biomarkers and Innovative Therapeutic Tools. Curr Drug Targets. 2016; 17:4:388397.
    [Google Scholar]
  8. Barton M. Aging and endothelin: determinants of disease. Life Sci. 2014; 118:2:97109.
    [Google Scholar]
  9. Kwak BR, Back M, Bochaton-Piallat ML, Caligiuri G, Daemen MJ, Davies PF, et al.  Biomechanical factors in atherosclerosis: mechanisms and clinical implications. Eur Heart J. 2014; 35:43:30133020, 20a-20d.
    [Google Scholar]
  10. Amini N, Boyle JJ, Moers B, Warboys CM, Malik TH, Zakkar M, et al.  Requirement of JNK1 for endothelial cell injury in atherogenesis. Atherosclerosis. 2014; 235:2:613618.
    [Google Scholar]
  11. Coleman PR, Chang G, Hutas G, Grimshaw M, Vadas MA, Gamble JR. Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells. Aging (Albany NY). 2013; 5:12:913924.
    [Google Scholar]
  12. Balaoing LR, Post AD, Liu H, Minn KT, Grande-Allen KJ. Age-related changes in aortic valve hemostatic protein regulation. Arterioscler Thromb Vasc Biol. 2014; 34:1:7280.
    [Google Scholar]
  13. Jansen F, Yang X, Nickenig G, Werner N, Vasa-Nicotera M. Role, Function and Therapeutic Potential of microRNAs in Vascular Aging. Curr Vasc Pharmacol. 2015; 13:3:324330.
    [Google Scholar]
  14. Hemmeryckx B, Hoylaerts MF, Deloose E, Van Hove CE, Fransen P, Bult H, et al.  Age-associated pro-inflammatory adaptations of the mouse thoracic aorta. Thromb Haemost. 2013; 110:4:785794.
    [Google Scholar]
  15. Granger DN, Rodrigues SF, Yildirim A, Senchenkova EY. Microvascular responses to cardiovascular risk factors. Microcirculation. 2010; 17:3:192205.
    [Google Scholar]
  16. Guide for the Care and Use of Laboratory Animals. The National Academies Collection: Reports funded by National Institutes of Health. Washington (DC) 2011.
  17. Bohlen HG, Gore RW. Preparation of rat intestinal muscle and mucosa for quantitative microcirculatory studies. Microvasc Res. 1976; 11:1:103110.
    [Google Scholar]
  18. Rippe B, Stelin G. Simulations of peritoneal solute transport during CAPD. Application of two-pore formalism. Kidney Int. 1989; 35::12341244.
    [Google Scholar]
  19. Rippe B, Stelin G, Haraldsson B. Computer simulations of peritoneal fluid transport in CAPD. Kidney Int. 1991; 40::315325.
    [Google Scholar]
  20. Flessner MF, Lofthouse J, Williams A. Increasing peritoneal contact area during dialysis improves mass transfer. J Am Soc Nephrol. 2001; 12:10:21392145.
    [Google Scholar]
  21. Flessner MF. Small-solute transport across specific peritoneal tissue surfaces in the rat. Journal of the American Society of Nephrology. 1996; 7::225233.
    [Google Scholar]
  22. Zakaria ER, Carlsson O, Rippe B. Limitation of small-solute exchange across the visceral peritoneum: effects of vibration. Perit Dial Int. 1997; 17::7279.
    [Google Scholar]
  23. Carlsson O, Rippe B. Enhanced peritoneal diffusion capacity of 51Cr-EDTA during the initial phase of peritoneal dialysis dwells: role of vasodilatation, dialysate ’stirring’, and of interstitial factors. Blood Purif. 1998; 16:3:162170.
    [Google Scholar]
  24. Favero G, Paganelli C, Buffoli B, Rodella LF, Rezzani R. Endothelium and its alterations in cardiovascular diseases: life style intervention. Biomed Res Int. 2014; 2014::801896.
    [Google Scholar]
  25. Esper RJ, Nordaby RA, Vilarino JO, Paragano A, Cacharron JL, Machado RA. Endothelial dysfunction: a comprehensive appraisal. Cardiovasc Diabetol. 2006; 5::4.
    [Google Scholar]
  26. Galley HF, Webster NR. Physiology of the endothelium. Br J Anaesth. 2004; 93:1:105113.
    [Google Scholar]
  27. Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. 2007; 100:2:158173.
    [Google Scholar]
  28. Feletou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol. 2006; 291:3:H9851002.
    [Google Scholar]
  29. Grover-Paez F, Zavalza-Gomez AB. Endothelial dysfunction and cardiovascular risk factors. Diabetes Res Clin Pract. 2009; 84:1:110.
    [Google Scholar]
  30. Brown MD. Endothelial ageing: molecular mechanisms and functional significance. Exp Physiol. 2009; 94:3:297298.
    [Google Scholar]
  31. Kozlov KL, Soldatov VM, Pal'tseva EM, Sedov EV, Poliakova VO, Lin'kova NS. [the Role of Endothelial Signal Molecules in Pathogenesis of Age-Associated Diseases]. Adv Gerontol. 2015; 28:1:2936.
    [Google Scholar]
  32. Kruse-Jarres R. Acquired bleeding disorders in the elderly. Hematology Am Soc Hematol Educ Program. 2015; 2015::231236.
    [Google Scholar]
  33. Park SY, Ives SJ, Gifford JR, Andtbacka RH, Hyngstrom JR, Reese V, et al.  Impact of age on the vasodilatory function of human skeletal muscle feed arteries. Am J Physiol Heart Circ Physiol. 2016; 310:2:H217H225.
    [Google Scholar]
  34. Su JB. Vascular endothelial dysfunction and pharmacological treatment. World J Cardiol. 2015; 7:11:719741.
    [Google Scholar]
  35. Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res. 2005; 66:2:286294.
    [Google Scholar]
  36. Gomez-Zamudio JH, Garcia-Macedo R, Lazaro-Suarez M, Ibarra-Barajas M, Kumate J, Cruz M. Vascular endothelial function is improved by oral glycine treatment in aged rats. Can J Physiol Pharmacol. 2015; 93:6:465473.
    [Google Scholar]
  37. Hashizume O, Ohnishi S, Mito T, Shimizu A, Ishikawa K, Nakada K, et al.  Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects. Sci Rep. 2015; 5::10434.
    [Google Scholar]
  38. Bonaccorsi R, Palla P, Tomasi J. Conformational energy of glycine in aqueous solutions and relative stability of the zwitterionic and neutral forms. An initio study. Jornal of the American Chemical Society. 1984; 94:3:2972978.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/qmj.2019.19
Loading
/content/journals/10.5339/qmj.2019.19
Loading

Data & Media loading...

  • Article Type: Research Article
Keyword(s): aging, glycine , endothelial cell , intravital microscopy and peritoneal microcirculation
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error