title: The role of nitric oxide in the reduction of protein kinase C-induced contractile response in aortae from rats with portal hypertension.
abstract: OBJECTIVE
  Protein kinase C plays a role in the regulation of vascular cell contraction but its activity may be reduced by nitric oxide. In portal hypertension, the exact mechanism by which nitric oxide induces vascular hyporeactivity to vasoconstrictors is unclear. The aim of this study was to investigate the role of the interaction of nitric oxide and protein kinase C in the vascular reactivity in isolated aortae from portal vein-stenosed rats.
  
  
  RESULTS
  The contractile response to phorbol 12,13-dibutyrate, a protein kinase C activator, was significantly reduced in portal vein-stenosed aortae compared to sham-operated aortae. Preincubation with N-nitro-L-arginine or endothelium removal enhanced the response to phorbol 12,13-dibutyrate. The hyporesponsiveness to phorbol 12,13-dibutyrate in portal vein-stenosed rat aortae was only corrected after endothelium removal. The time course of contractions induced by phorbol 12,13-dibutyrate showed that the contraction was maintained for 2 h in sham-operated aortae and decreased to baseline in portal vein-stenosed rat aortae. This decrease was inhibited by N-nitro-L-arginine preincubation or endothelium removal. Protein kinase C downregulation caused a more marked reduction of phenylephrine-induced contraction in portal vein-stenosed aortae than in sham-operated aortae. The time course of total nitric oxide synthase activity in the presence of phorbol 12,13-dibutyrate showed a decrease in nitric oxide synthase activity after 30 min in both groups. Nitric oxide synthase activity remained stable for 120 min in sham-operated aortae but returned to basal level in portal vein-stenosed aortae.
  
  
  CONCLUSIONS
  Hyporeactivity to vasoconstrictors in portal vein-stenosed rat aortae may be due, in part, to a decrease in protein kinase C activation caused by nitric oxide overproduction.
authors.affiliation: Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-481, Hôpital Beaujon, Clichy, France.
authors.forename: C
authors.initials: C
authors.lastname: Chagneau
authors.forename: K A
authors.initials: KA
authors.lastname: Tazi
authors.forename: J
authors.initials: J
authors.lastname: Heller
authors.forename: P
authors.initials: P
authors.lastname: Sogni
authors.forename: O
authors.initials: O
authors.lastname: Poirel
authors.forename: R
authors.initials: R
authors.lastname: Moreau
authors.forename: D
authors.initials: D
authors.lastname: Lebrec
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D015536:Down-Regulation / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D015240:Phorbol 12,13-Dibutyrate; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C