Influence of diabetes mellitus, hypercholesterolemia, and their combination on EDHF-mediated responses in mice

Keiko Morikawa, Tetsuya Matoba, Hiroshi Kubota, Makoto Hatanaka, Takako Fujiki, Shosuke Takahashi, Akira Takeshita, Hiroaki Shimokawa

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The endothelium synthesizes and releases several vasodilator substances, including vasodilator prostaglandins, NO, and EDHF. NO-mediated relaxations are reduced by various risk factors, such as diabetes mellitus and hypercholesterolemia. However, it remains to be elucidated whether EDHF-mediated relaxations also are reduced by those factors and their combination. In this study, we addressed this point in mice. We used small mesenteric arteries from control, diabetic (streptozotocin-induced), apolipoprotein-E-deficient (ApoE-/-), and diabetic ApoE-/- mice. In control mice, endothelium-dependent relaxations to acetylcholine were largely mediated by EDHF. This EDHF-mediated component was slightly reduced in diabetic mice, preserved in ApoE-/- mice, and markedly reduced in diabetic ApoE -/- mice with an increase in NO-mediated component and a negative contribution of indomethacin-sensitive endothelium-derived contracting factor (EDCF). Endothelium-independent relaxations to sodium nitroprusside or NS1619, a direct opener of calcium-activated K channels, were attenuated in ApoE -/- and diabetic ApoE-/- mice. Endothelium-dependent hyperpolarizations were significantly reduced in diabetic mice, preserved in ApoE-/- mice, and again markedly reduced in diabetic ApoE -/- mice. These results indicate that hypercholesterolemia alone minimally affects the EDHF-mediated relaxations, and diabetes mellitus significantly attenuated the responses, whereas their combination markedly attenuates the responses with a compensatory involvement of NO and a negative contribution of EDCF.

Original languageEnglish
Pages (from-to)485-490
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume45
Issue number5
DOIs
Publication statusPublished - May 1 2005

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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