Upregulation of endothelium-derived hyperpolarizing factor compensates for the loss of nitric oxide in mesenteric arteries of dahl salt-sensitive hypertensive rats

Kenichi Goto, Yasuo Kansui, Hideyuki Oniki, Toshio Ohtsubo, Kiyoshi Matsumura, Takanari Kitazono

研究成果: ジャーナルへの寄稿記事

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This study was designed to determine whether a high-salt diet would alter endothelial function and, if so, the relative contributions of endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide (NO) to any changes in vasomotor responses. Male Dahl salt-sensitive (DS) rats were given either a high-salt diet (8% NaCl, DS-H) or a low-salt diet (0.4% NaCl, DS-L) for 6 weeks. Membrane potentials and contractile responses were recorded from the isolated superior mesenteric arteries. After salt loading, DS-H developed hypertension, while DS-L remained normotensive. No difference was found in acetylcholine (ACh)-induced, endothelium-dependent relaxation between the groups. However, after treatment with indomethacin and NO synthase inhibitor, EDHF-like relaxation was significantly greater in DS-H than in DS-L. In contrast, NO-mediated relaxation was significantly smaller in DS-Hthan in DS-L. Iberiotoxin (IbTx), a specific blocker of large-conductance calcium-dependent potassium (BKCa) channels, attenuated EDHF-like relaxation in DS-H but not in DS-L. IbTx marginally inhibited EDHF-mediated hyperpolarization only in DS-H. Endothelium-independent relaxation in response to sodium nitroprusside or levcromakalim was similar in both groups. In conclusion, EDHF-like relaxation is upregulated through the activation of BKCa channels in the mesenteric arteries of DS-H. As the overall relaxation in response to ACh did not differ between the groups, the upregulation of EDHF appears to compensate for the loss of NO in the mesenteric arteries of DS-H.

元の言語英語
ページ(範囲)849-854
ページ数6
ジャーナルHypertension Research
35
発行部数8
DOI
出版物ステータス出版済み - 8 1 2012

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All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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