title: Nitric oxide is an autocrine feedback inhibitor of vascular smooth muscle contraction.
abstract: BACKGROUND
  Substances that increase intracellular calcium ([Ca2+]i), such as potassium chloride and serotonin, are known to induce vascular smooth muscle (VSM) contraction. One form of nitric oxide synthase, which converts L-arginine to nitric oxide, exists as a Ca(2+)-calmodulin dependent enzyme. The objective of this study was to determine whether agonists that induce VSM contraction by increasing [Ca2+]i might also activate Ca(2+)-calmodulin dependent nitric oxide synthase in VSM.
  
  
  METHODS
  Strips of bovine carotid arterial smooth muscle denuded of endothelium were equilibrated in a physiologic muscle bath. A maximal contractile response to high extracellular potassium chloride and serotonin was established. The strips were then preincubated with NG-monomethyl-L-arginine (L-NMMA), a structural analog of L-arginine and specific inhibitor of nitric oxide synthase, and again treated with either KCl or 5-hydroxytryptamine.
  
  
  RESULTS
  The contractile responses of muscle strips to KCl or 5-hydroxytryptamine were significantly greater in muscle strips pretreated with L-NMMA than responses in the absence of L-NMMA (p < 0.02, Student's t test). To determine whether this response was Ca2+ dependent, phorbolester-induced contractions in Ca(2+)-free conditions were examined. No difference was noted in the magnitude of Ca(2+)-free, phorbol ester-induced contractions in the presence and absence of L-NMMA.
  
  
  CONCLUSIONS
  These data thus suggest that Ca(2+)-calmodulin dependent nitric oxide synthase is functionally present in VSM and may function as an autocrine regulatory mechanism of VSM contraction.
authors.affiliation: Medical College of Georgia School of Medicine, Department of Surgery, Augusta, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Yeh
authors.forename: E G
authors.initials: EG
authors.lastname: Whitney
authors.forename: S
authors.initials: S
authors.lastname: Lamb
authors.forename: C M
authors.initials: CM
authors.lastname: Brophy
mesh_terms: D000818:Animals; D002417:Cattle; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D017366:Serotonin Receptor Agonists; D009569:Nitric Oxide; D012701:Serotonin; D011189:Potassium Chloride