Sepsis alters vessel contraction by adrenoceptor-induced nitric oxide and prostanoid

Touichi Kawabe, Patrick D. Harris, E. L.Rasheid Zakaria, R. Neal Garrison

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background. Alpha-adrenergic agents contract vascular smooth muscle (VSM) and stimulate endothelial release of secondary factors which modulate VSM contraction. Our study examined constrictor prostanoid (cPN) and nitric oxide (NO) as secondary factors which could alter alpha-1 adrenoceptor-mediated contraction during sepsis. Methods. Sepsis was induced in rats by inoculation of an implanted sponge with Escherichia coli and Bacteroides fragilis. Aortic rings at 24 h from septic (n = 21) and control (n = 21) rats were suspended in physiological salt solution (PSS) with or without blockers to NO (NG-monomethylarginine), cPN (mefenamic acid, MFA), or thromboxane A2 (SQ29548). Contraction dose-response curves were generated to determine maximal contraction force (Fmax) and pD2 (sensitivity) to phenylephrine in each experimental group. Results. Sepsis increased Fmax to phenylephrine (PHE) (1.18 vs 0.90 g, SEM 0.0703). COX inhibition reduced the Fmax in control (0.63 vs 0.90 g, SEM 0.0675) but not in septic animals (1.19 vs 1.18 g, SEM 0.0433). TXA2 receptor inhibition did not alter Fmax in control (1.017 vs 0.973 g, SEM 0.0959) or septic animals (1.28 vs 1.12 g, SEM 0.0823). NOS inhibition enhanced the Fmax in both nonseptic (2.03 vs 0.83 g, SEM 0.0523) and septic rats (1.96 vs 1.15 g, SEM 0.0526), but did less so in the septic animals. Conclusions. PHE-induced Fmax is determined by a balance between PHE-stimulated VSM alpha-adrenoceptor activity, and PHE-stimulated endothelial release of cPN and NO. Sepsis enhances total PHE-induced Fmax by increasing VSM alpha-adrenoceptor activity and reducing PHE-stimulated endothelial release of dilator NO. Sepsis abolishes the PHE-stimulated endothelial release of cPN. PHE-stimulated cPN is not thromboxane A2, but could be a nonprostanoid dilator in the lipoxygenase (HETE) or cytochrome P450 (EET) pathways.

Original languageEnglish (US)
Pages (from-to)352-359
Number of pages8
JournalJournal of Surgical Research
Volume110
Issue number2
DOIs
StatePublished - Apr 2003
Externally publishedYes

Keywords

  • Alpha-adrenoceptor
  • Aortic rings
  • Endothelial factors
  • L-NMMA
  • MFA
  • Nitric oxide
  • Phenylephrine

ASJC Scopus subject areas

  • Surgery

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