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Elevated vascular γ‐butyrobetaine levels attenuate the development of high glucose‐induced endothelial dysfunction
Author(s) -
Vilskersts Reinis,
ZharkovaMalkova Olga,
Mezhapuke Rudolfs,
Grinberga Solveiga,
Cirule Helena,
Dambrova Maija
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12127
Subject(s) - carnitine , endothelial dysfunction , endocrinology , medicine , lysophosphatidylcholine , vascular tissue , chemistry , biology , biochemistry , phospholipid , botany , membrane , phosphatidylcholine
Summary The aim of the present study was to investigate the effects of vascular tissue levels of l ‐carnitine and its precursor, γ‐butyrobetaine ( GBB ), on the development of endothelial dysfunction induced by 5 μmol/L lysophosphatidylcholine ( LPC ), 10 mmol/L triglycerides ( TG ) or a high glucose concentration (44 mmol/L). Changes in vascular tissue levels of l ‐carnitine and GBB were induced by administration of l ‐carnitine (100 mg/kg), mildronate (100 mg/kg; an inhibitor of l ‐carnitine synthesis) or their combination to male Wistar rats for 2 weeks. Treatment with l ‐carnitine elevated vascular tissue levels of l ‐carnitine, whereas administration of mildronate reduced l ‐carnitine levels and increased GBB levels. Experimental animals that received the combination of both drugs showed elevated tissue levels of GBB . The results from organ bath experiments demonstrated that increased GBB levels with preserved l ‐carnitine content in vascular tissues attenuated the development of endothelial dysfunction induced by high glucose. However, changes in vascular tissue l ‐carnitine and GBB levels had no impact on endothelial dysfunction induced by TG or LPC . The results demonstrate that increased levels of GBB with preserved l ‐carnitine content in vascular tissue attenuate the development of endothelial dysfunction induced by high glucose concentrations.