title: Sepsis alters vessel contraction by adrenoceptor-induced nitric oxide and prostanoid.
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 (N(G)-monomethylarginine), cPN (mefenamic acid, MFA), or thromboxane A2 (SQ29548). Contraction dose-response curves were generated to determine maximal contraction force (F(max)) and pD2 (sensitivity) to phenylephrine in each experimental group.
  
  
  RESULTS
  Sepsis increased F(max) to phenylephrine (PHE) (1.18 vs 0.90 g, SEM 0.0703). COX inhibition reduced the F(max) 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 F(max) 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 F(max) 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 F(max) 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 F(max) 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.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine HSC-1115, University of Louisville, Louisville, KY 40292, USA. tksmile@bellsouth.net
authors.forename: Touichi
authors.initials: T
authors.lastname: Kawabe
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Harris
authors.forename: E L Rasheid
authors.initials: EL
authors.lastname: Zakaria
authors.forename: R Neal
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D001442:Bacteroides Infections / Q000378:metabolism / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D013928:Thromboxane A2; D019001:Nitric Oxide Synthase