Induction of heme oxygenase-1 with hemoglobin depresses vasoreactivity in rat aorta

Sean P. Gaine, Greg Booth, Leo Otterbein, Nicholas A. Flavahan, Augustine M.K. Choi, Charles M. Wiener

Research output: Contribution to journalArticle

Abstract

Septic shock induced by lipopolysaccharide (LPS) produces systemic hypotension and decreased responsiveness to vasoconstrictors. Recently, intravenous injection of hemoglobin (HGB) into rats was found to be protective from a subsequent lethal dose of LPS and was correlated with induction of the enzyme heme oxygenase-1 (HO-1). To determine whether the HGB modulated the vasomotor tone of systemic arteries, we evaluated the effect of in vivo treatment with HGB and LPS on vasoconstrictor responses to phenylephrine (PE) in the isolated rat aorta. Rats (n = 4, for each group) were injected intravenously with rat HGB (200 mg/kg i.v.) or normal saline control (CON) 16 h before sacrifice, and/or LPS (20 mg/kg) or CON 4 h before sacrifice. The descending aorta was dissected into rings and suspended in a modified Krebs solution where vasoconstrictor responses were determined to KCl (60 mM) and PE (10-8 to 10-5 M). LPS, but not HGB, inhibited the vasoconstrictor response to KCl. LPS, HGB, and HGB+LPS inhibited the maximal vasoconstrictor response to PE (PE(max)). Induction of HO-1 RNA in the aorta by HGB and by LPS was demonstrated by Northern blot analysis. To determine if induction of HO-1 was related to the effect of LPS or HGB on vascular reactivity, vessels were treated with the HO-1 inhibitor, SnPP9 (30 νM). PE(max) in SnPP9+HGB vessels was not different from control, whereas SnPP9+LPS vessels had a marked decrease in PE(max). We conclude that induction of HO-1 does not protect the rat aorta from the vasodepressor effects of LPS in vitro. Our results demonstrate, however, that the induction of HO-1 causes vasodepression, possibly via increased production of carbon monoxide.

Original languageEnglish (US)
Pages (from-to)114-119
Number of pages6
JournalJournal of Vascular Research
Volume36
Issue number2
DOIs
StatePublished - Jan 1 1999

Keywords

  • Aorta, rat
  • Carbon monoxide
  • Heme oxygenase
  • Lipopolysaccharide
  • Septic shock
  • Vascular reactivity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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