title: Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension.
abstract: OBJECTIVE
  Vascular hyporeactivity to vasoconstrictors contributes to splanchnic arterial vasodilatation and hemodynamic dysregulation in portal hypertension. Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to improve adrenergic vascular contractility in portal hypertensive rats and markedly attenuate hyperdynamic circulation. To further characterize the NPY-effects in portal hypertension, we investigated its role for non-receptor-mediated vasoconstriction in the superior mesenteric artery (SMA) of portal vein ligated (PVL) and sham-operated rats.
  
  
  METHODS
  Ex vivo SMA perfusion of PVL and sham rats was used to analyse the effects of NPY on pressure response to non-receptor-mediated vasoconstriction. Dose-response curves to KCl (30-300 mM) were used to bypass G protein-coupled receptor mechanisms. Potential involvement of the cyclooxygenase-pathway was tested by non-selective cyclooxygenase-inhibition using indomethacin.
  
  
  RESULTS
  KCl-induced vascular contractility but not vascular sensitivity was significantly attenuated in PVL rats as compared with sham rats. Administration of NPY resulted in an augmentation of KCl-evoked vascular sensitivity being not different between study groups. However, KCl-induced vascular contractility was markedly more enhanced in PVL rats, thus, vascular response was no more significantly different between PVL and sham rats after addition of NPY. Administration of indomethacin abolished the NPY-induced enhancement of vasoconstriction.
  
  
  CONCLUSIONS
  Receptor-independent vascular contractility is impaired in mesenteric arteries in portal hypertension. NPY improves non-receptor mediated mesenteric vasoconstriction more effective in portal hypertension than in healthy conditions correcting splanchnic vascular hyporesponsiveness. This beneficial vasoactive action of NPY adds to its well known more pronounced effects on adrenergic vasoconstriction in portal hypertension making it a promising therapeutic agent in portal hypertension.
authors.affiliation: First Medical Center University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hartl
authors.affiliation: Department of Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dietrich
authors.affiliation: Department of Internal Medicine, University Medical Center, Regensburg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Moleda
authors.affiliation: Department of Internal Medicine, University Medical Center, Regensburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Müller-Schilling
authors.affiliation: Department of Visceral Surgery and Medicine, Bern University Hospital Inselspital, Bern, Switzerland.
authors.forename: Reiner
authors.initials: R
authors.lastname: Wiest
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009478:Neuropeptide Y / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D013152:Splanchnic Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D014662:Vasoconstrictor Agents; D011189:Potassium Chloride; D007213:Indomethacin
keywords: Neuropeptide Y; cirrhosis; hyperdynamic circulatory syndrome; portal hypertension; splanchnic vasodilatation; vasoconstriction