Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca 2+ signaling and NO production in rat aorta

Jiaxuan Zhu, Ines Drenjancevic-Peric, Scott McEwen, Jill Friesema, Danielle Schulta, Ming Yu, Richard J. Roman, Julian H. Lombard

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or changed to a high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular Ca 2+ ([Ca 2+] i) in response to methacholine (10 μM) and histamine (10 μM) were significantly attenuated in aortic endothelial cells from rats fed a HS diet, whereas thapsigargin (10 μM)-induced increases in [Ca 2+] i were unaffected. Methacholine-induced nitric oxide (NO) production was eliminated in endothelial cells of aortas from rats fed a HS diet. Low-dose ANG II infusion (5 ng·kg -1·min -1 iv) for 3 days prevented impaired [Ca 2+] i signaling response to methacholine and histamine and restored methacholine-induced NO production in aortas from rats on a HS diet. Adding Tempol (500 μM) to the tissue bath to scavenge superoxide anions increased NO release and caused N ω-nitro-L-arginine methyl ester-sensitive vascular relaxation in aortas from rats fed a HS diet but had no effect on methacholine-induced Ca 2+ responses. Chronic treatment with Tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased methacholine-induced Ca 2+ responses significantly in aortas from rats on a HS diet but not in aortas from rats on a LS diet. These findings suggest that 1) agonist-induced Ca 2+ responses and NO levels are reduced in aortas of rats on a HS diet; 2) increased vascular superoxide levels contribute to NO destruction, and, eventually, to impaired Ca 2+ signaling in the vascular endothelial cells; and 3) reduced circulating ANG II levels during elevated dietary salt lead to elevated superoxide levels, impaired endothelial Ca 2+ signaling, and reduced NO production in the endothelium.

Original languageEnglish (US)
Pages (from-to)H929-H938
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number2
DOIs
StatePublished - 2006

Keywords

  • Dietary salt intake
  • Endothelium
  • Nitric oxide
  • Sodium
  • Vascular relaxation

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