Eicosapentaenoic Acid Improves Imbalance between Vasodilator and Vasoconstrictor Actions of Endothelium-Derived Factors in Mesenteric Arteries from Rats at Chronic Stage of Type 2 Diabetes

• DOI: 10.1124/jpet.108.148718
• Publication Date: 2009-01-23T02:12:21Z
• Authors: Takayuki Matsumoto; Naoaki Nakayama; Keiko Ishida; Tsuneo Kobayashi; Katsuo Kamata
• Keywords: Endothelial Dysfunction; Endothelium-derived hyperpolarizing factor; Mesenteric arteries

Accumulating evidence demonstrates that dietary intake of <i>n</i>-3 polyunsaturated fatty acids (PUFAs) is associated with a reduced incidence several cardiovascular diseases involve endothelial dysfunction. However, the molecular mechanism remains unclear. We previously reported mesenteric arteries from type 2 diabetic Otsuka Long-Evans Tokushima (OLETF) rats exhibit dysfunction, leading to an imbalance between endothelium-derived vasodilators [namely, nitric oxide (NO) and hyperpolarizing factor (EDHF)] vasoconstrictors [endothelium-derived contracting factors (EDCFs)] [namely cyclooxygenase (COX)-derived prostanoids] (<i>Am J Physiol Heart Circ Physiol</i> 293:H1480–H1490, 2007). hypothesized treating OLETF eicosapentaenoic acid (EPA), major PUFA, may improve dysfunction by correcting this imbalance. In [compared age-matched control (LETO) rats]: 1) acetylcholine (ACh)-induced (endothelium-dependent) relaxation was impaired, 2) NO- EDHF-mediated relaxations nitrite production were reduced, 3) ACh-induced EDCF-mediated contraction, prostanoids, protein expressions COX-1 COX-2 all increased. When received chronic EPA treatment long-term (300 mg/kg/day p.o. for 4 weeks), their isolated exhibited: improvements in COX-mediated EDCF- arachidonic acid-induced contractions, normalized NO metabolism, 4) suppressed 5) expression, 6) phosphoextracellular signal-regulated kinase (ERK) expression. Moreover, both ERK2 nuclear (NF)-κB activities aortas. propose ameliorates factors, at least partly, inhibiting ERK, decreasing NF-κB activation, reducing