Abnormal activation of Na+-K+ pump in aortas from rats with endotoxaemia

Shiu Jen Chen, Kao Hsiang Chen, R. Clinton Webb, Mao Hsiung Yen, Chin Chen Wu

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

A diminished reactivity to several vasoconstrictor agents is usually observed in blood vessels obtained from animals with endotoxic shock. The contractile state of vascular smooth muscle is influenced by the activity of the electrogenical sodium (Na+-K+) pump. Thus, we examined inhibitors and agonists of nitric oxide (NO)-guanosine 3′:5′-cyclic monophosphate (cGMP) on contractions to phenylephrine (PE) and relaxations to potassium in isolated aortic segments from rats treated with bacterial endotoxin (lipopolysaccharide, LPS) for 6 h (i.e. to mimic a shock syndrome). Endotoxaemia for 6 h was associated with a severe hypotension and vascular hyporeactivity to noradrenaline and an increased plasma nitrate level in vivo. The PE-induced contraction was attenuated in aortic smooth muscle obtained from rats with endotoxic shock while the potassium-induced relaxation was greater in these preparations. Ouabain dose-dependently inhibited the potassium-induced relaxation in aortas from normal and endotoxaemic rats. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one enhanced the PE-induced contraction in endotoxaemic rats only, whereas it attenuated the difference of potassium-induced relaxation between normal and endotoxaemic rats. In contrast, in aortas obtained from normal rats, 8-bromo-cGMP reduced the PE-induced contraction and enhanced the potassium-induced relaxation to the level as seen in endotoxaemic animals. In aortas obtained from endotoxaemic rats, methylene blue further restored the PE-induced contraction to the normal and abolished the difference of potassium-induced relaxation between normal and endotoxaemic rats. These results suggest that the Na+-K+ pump in the vascular bed of animals with endotoxic shock is abnormally activated and this augmented activation is modulated by cGMP.

Original languageEnglish (US)
Pages (from-to)57-62
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume368
Issue number1
DOIs
StatePublished - Aug 1 2003

Keywords

  • Endotoxin
  • Na-K pump
  • Ouabain
  • Potassium-induced relaxation
  • cGMP

ASJC Scopus subject areas

  • Pharmacology

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