Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 535, Issue 1-3, Pages 228-233Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2006.01.063
Keywords
diabetes; rat mesenteric bed; endothelium; streptozotocin; lovastatin; chelerythrine
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Diabetes mellitus is associated with an increased risk of cardiovascular disease. Endothelial dysfunction (i.e. decreased endothelium-dependent vasorelaxation) plays a key role in the pathogenesis of diabetic vascular disease. The present study was undertaken to determine whether diabetes induced by streptozotocin alters mesenteric responses to vasodilators and, if so, to study the acute in vitro effects of lovastatin and chelerythrine. Endothelial function was assessed in constantly perfused preparation removed from rats, 12 weeks after treatment with either saline or streptozotocin (45 mg/kg, intraperitoneally). In pre-contracted mesenteric beds (with 100 mu M phenylephrine) removed from diabetic rats, the concentration response curve to acetylcholine, but not to sodium nitroprusside, was significantly reduced. Perfusion with lovastatin (10 mu M for 20 min) or chelerythrine (1 mu M for 20 min) significantly improved the acetylcholine-mediated relaxation in preparations removed from diabetic but not control rats. Pre-incubation of tissue with N-G-nitro-L-argenine methyl ester hydrochloride (10 mu M for 20 min) inhibited the beneficial effect of lovastatin but not chelerythrine. Pre-treatment of tissue with indomethacin (10 mu M for 20 min) did not modify the effects of lovastatin or chelerythrine on acetylcholine responses. The present results demonstrate that endothelial dysfunction induced by diabetes (in a resistant vasculature, such as rat mesenteric bed) may be improved by an acute exposure to either lovastatin or chelerythrine. Furthermore, our results suggest that the beneficial effect of lovastatin is mediated via the nitric oxide pathway. (c) 2006 Elsevier B.V. All rights reserved.
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