Extracellular alkalinization induces endothelium-derived nitric oxide dependent relaxation in rat thoracic aorta

A. C. Celotto, V. K. Capellini, C. B A Restini, C. F. Baldo, L. M. Bendhack, P. R B Evora

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Aim: To investigate the mechanism through which the extracellular alkalinization promotes relaxation in rat thoracic aorta. Methods: The relaxation response to NaOH-induced extracellular alkalinization (7.4-8.5) was measured in aortic rings pre-contracted with phenylephrine (Phe, 10-6M). The vascular reactivity experiments were performed in endothelium-intact and -denuded rings, in the presence or and absence of indomethacin (10-5M), NG-nitro-l-arginine methyl ester (L-NAME, 10-4M), N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide/HCl (W-7, 10-7M), 2,5-dimethylbenzimidazole (DMB, 2×10-5 M) and methyl-β-cyclodextrin (10-2M). In addition, the effects of NaOH-induced extracellular alkalinization (pH 8.0 and 8.5) on the intracellular nitric oxide (NO) concentration was evaluated in isolated endothelial cells loaded with diaminofluorescein-FM diacetate (DAF-FM DA, 5μM), in the presence and absence of DMB (2×10-5 M). Results: The extracellular alkalinization failed to induce any change in vascular tone in aortic rings pre-contracted with KCl. In rings pre-contracted with Phe, the extracellular alkalinization caused relaxation in the endothelium-intact rings only, and this relaxation was maintained after cyclooxygenase inhibition; completely abolished by the inhibition of nitric oxide synthase (NOS), Ca2+/calmodulin and Na+/Ca2+ exchanger (NCX), and partially blunted by the caveolae disassembly. Conclusions: These results suggest that, in rat thoracic aorta, that extracellular alkalinization with NaOH activates the NCX reverse mode of endothelial cells in rat thoracic aorta, thereby the intracellular Ca2+ concentration and activating the Ca2+/calmodulin-dependent NOS. In turn, NO is released promoting relaxation.

Original languageEnglish (US)
Pages (from-to)269-274
Number of pages6
JournalNitric Oxide - Biology and Chemistry
Volume23
Issue number4
DOIs
StatePublished - Dec 15 2010

Keywords

  • Alkalinization
  • Endothelium
  • Nitric oxide
  • Rat aorta
  • Relaxation

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