Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension

Hartl J, Dietrich P, Moleda L, Mueller-Schilling M, Wiest R (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Liver International Wiley-Blackwell

Publisher: Wiley-Blackwell

Book Volume: 35

Pages Range: 2556-63

Journal Issue: 12

DOI: 10.1111/liv.12874

Abstract

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.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.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.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 with CRIS profile

Peter Dietrich Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Inselspital, Universitätsspital Bern CH Switzerland (CH)

How to cite

APA:

Hartl, J., Dietrich, P., Moleda, L., Mueller-Schilling, M., & Wiest, R. (2015). Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension. Liver International, 35(12), 2556-63. https://doi.org/10.1111/liv.12874

MLA:

Hartl, Johannes, et al. "Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension." Liver International 35.12 (2015): 2556-63.

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