title: Hyperkinetic circulation and decreased sensitivity to vasoconstrictors following portacaval shunt in the rat. Effects of chronic nitric oxide inhibition.
abstract: OBJECTIVE
  This study aimed to investigate: (i) whether the hyperkinetic circulation that develops after portacaval shunt is associated with decreased vascular sensitivity to vasoconstrictors and (ii) the role of nitric oxide on its pathogenesis.
  
  
  METHODS
  Portacaval-shunted and sham-operated rats received long-term treatment with the nitric oxide inhibitor L-NAME (osmotic minipump) or its inactive enantiomer D-NAME. Measurements of arterial pressure, cardiac output and superior mesenteric artery blood flow (transit-time flow probe) were done 4 days later in baseline conditions and after increasing doses of methoxamine. Peripheral and superior mesenteric vascular resistance were calculated.
  
  
  RESULTS
  Portacaval shunted rats showed a significantly lower peripheral and superior mesenteric vascular resistance and a significant reduction in their response to incremental doses of methoxamine than sham-operated controls. Chronic nitric oxide inhibition attenuated the systemic but not the splanchnic vasodilatation and totally corrected the hyposensitivity to methoxamine of portacaval-shunted rats. However, they still had a significantly lower peripheral and superior mesenteric vascular resistance than sham-operated rats.
  
  
  CONCLUSIONS
  This study shows that the splanchnic and systemic hyporesponsiveness to methoxamine observed in portacaval-shunted rats could be explained by an excess of nitric oxide. However, other factors may be involved in maintaining splanchnic and systemic vasodilatation despite NO-inhibition.
authors.affiliation: Department of Medicine, Institut de Investigació Biomèdica August Pi i Sunyer, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Bandi
authors.forename: M
authors.initials: M
authors.lastname: Fernández
authors.forename: C
authors.initials: C
authors.lastname: Bernadich
authors.forename: A M
authors.initials: AM
authors.lastname: De Lacy
authors.forename: J C
authors.initials: JC
authors.lastname: García-Pagán
authors.forename: J
authors.initials: J
authors.lastname: Bosch
authors.forename: J
authors.initials: J
authors.lastname: Rodés
mesh_terms: D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011167:Portacaval Shunt, Surgical; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D013237:Stereoisomerism; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D005934:Glucagon; D008729:Methoxamine; D019331:NG-Nitroarginine Methyl Ester