Augmentation of NO-mediated vasodilation in metabolic acidosis

Kaoru Hattori, Shinya Tsuchida, Hirokazu Tsukahara, Mitsufumi Mayumi, Takashi Tanaka, Li Zhang, Takanobu Taniguchi, Ikunobu Muramatsu

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Reduction of perivascular pH in acidemia produces hyporesponsiveness of vascular bed to vasoconstrictors. In the present study, we examined the effects of modest acidification on dilatory responses of isolated rat thoracic aorta. Acetylcholine produced endothelium-dependent relaxation in phenylephrine-precontracted aorta, which was markedly enhanced by acidification of Krebs-Henseleit solution from pH 7.4 to 7.0. A similar augmentation was observed in the relaxing responses to NO donors (SNP, SIN-1, SNAP), 8-Br-cGMP and NS-1619 (a putative KCa channel opener and/or Ca channel inhibitor) in endothelium-denuded, phenylephrine-contracted aorta. However, papaverine-induced relaxation was not affected by the change in pH. At pH 7.4, the relaxing responses to acetylcholine and SNP were partially inhibited by charybdotoxin (KCa channel inhibitor) but not glibenclamide (KATP channel inhibitor), while at pH 7.0 the relaxation induced by either drug was not affected by K+ channel inhibitors. Relaxation induced by 8-Br-cGMP or NS-1619 was not inhibited by charybdotoxin or glibenclamide. Acidification to pH 7.0 increased the cGMP production in response to acetylcholine in endothelium-intact aorta and to SNP in endothelium-denuded aorta. These results show that modest acidification augments NO-mediated relaxation in rat aorta, probably due to an enhancement of cGMP-dependent but K+ channel-unrelated relaxation mechanisms.

Original languageEnglish
Pages (from-to)1439-1447
Number of pages9
JournalLife Sciences
Volume71
Issue number12
DOIs
Publication statusPublished - Aug 9 2002
Externally publishedYes

Keywords

  • Acidification
  • Nitric oxide (NO)
  • Rat aorta
  • Vasorelaxation
  • cGMP

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Hattori, K., Tsuchida, S., Tsukahara, H., Mayumi, M., Tanaka, T., Zhang, L., Taniguchi, T., & Muramatsu, I. (2002). Augmentation of NO-mediated vasodilation in metabolic acidosis. Life Sciences, 71(12), 1439-1447. https://doi.org/10.1016/S0024-3205(02)01914-8