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Amelioration of portal hypertension and the hyperdynamic circulatory syndrome in cirrhotic rats by neuropeptide Y via pronounced splanchnic vasoaction.
Gut. 2011 Aug; 60(8):1122-32.Gut

Abstract

BACKGROUND

Splanchnic vasodilation triggers the development of the hyperdynamic circulatory syndrome in portal hypertension. Neuropeptide Y (NPY), a sympathetic co-transmitter of norepinephrine, improves contractility in mesenteric arteries of pre-hepatic portal hypertensive rats. Therefore, we investigated the effect of NPY on mesenteric arterial contractility in vitro and in vivo in cirrhotic ascitic rats, as well as the vasoactive pathways involved.

METHODS

All experiments were performed in CCl₄-induced cirrhotic rats with ascites and compared to controls. In vivo haemodynamic characterisation was assessed before and after cumulative application of NPY i.v. using the microspheres technique. In vitro mesenteric arterial perfusion was used to analyse the effect of NPY on the response to α₁-adrenergic, as well as nitrergic stimulation. The NPY effects on vasoactive pathways (RhoA/Rho-kinase and NOS/NO) were analysed by western blot in mesenteric arteries.

RESULTS

NPY decreased portal-venous blood flow and reduced portal pressure in cirrhotic rats, without changes in mean arterial pressure. This was accompanied by decreased cardiac output and normalised systemic vascular resistance in cirrhotic rats. By contrast, no significant splanchnic or systemic haemodynamic effect of NPY was seen in controls. NPY enhanced arterial contractility in cirrhotic but not in control rats. Furthermore, NO-mediated vasodilation was reduced to a greater extent than in controls. These findings were paralleled by an increased expression and activity of the constrictive Rho-kinase pathway and decreased activation of vasodilating NOS/NO signalling after NPY administration in mesenteric arteries.

CONCLUSIONS

NPY exerts marked portal hypotensive effects and ameliorates the hyperdynamic circulation in cirrhotic ascitic rats. This is mediated mainly by a pronounced splanchnic vasoconstriction and reduction in splanchnic blood flow due to enhanced Rho-kinase expression and activity, as well as reduced NOS activation and NO effect.

Authors+Show Affiliations

Department of Internal Medicine, University Medical Center, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21317421

Citation

Moleda, Lukas, et al. "Amelioration of Portal Hypertension and the Hyperdynamic Circulatory Syndrome in Cirrhotic Rats By Neuropeptide Y Via Pronounced Splanchnic Vasoaction." Gut, vol. 60, no. 8, 2011, pp. 1122-32.
Moleda L, Trebicka J, Dietrich P, et al. Amelioration of portal hypertension and the hyperdynamic circulatory syndrome in cirrhotic rats by neuropeptide Y via pronounced splanchnic vasoaction. Gut. 2011;60(8):1122-32.
Moleda, L., Trebicka, J., Dietrich, P., Gäbele, E., Hellerbrand, C., Straub, R. H., Sauerbruch, T., Schoelmerich, J., & Wiest, R. (2011). Amelioration of portal hypertension and the hyperdynamic circulatory syndrome in cirrhotic rats by neuropeptide Y via pronounced splanchnic vasoaction. Gut, 60(8), 1122-32. https://doi.org/10.1136/gut.2010.226407
Moleda L, et al. Amelioration of Portal Hypertension and the Hyperdynamic Circulatory Syndrome in Cirrhotic Rats By Neuropeptide Y Via Pronounced Splanchnic Vasoaction. Gut. 2011;60(8):1122-32. PubMed PMID: 21317421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amelioration of portal hypertension and the hyperdynamic circulatory syndrome in cirrhotic rats by neuropeptide Y via pronounced splanchnic vasoaction. AU - Moleda,Lukas, AU - Trebicka,Jonel, AU - Dietrich,Peter, AU - Gäbele,Erwin, AU - Hellerbrand,Claus, AU - Straub,Rainer H, AU - Sauerbruch,Tilman, AU - Schoelmerich,Juergen, AU - Wiest,Reiner, Y1 - 2011/02/12/ PY - 2011/2/15/entrez PY - 2011/2/15/pubmed PY - 2011/11/9/medline SP - 1122 EP - 32 JF - Gut JO - Gut VL - 60 IS - 8 N2 - BACKGROUND: Splanchnic vasodilation triggers the development of the hyperdynamic circulatory syndrome in portal hypertension. Neuropeptide Y (NPY), a sympathetic co-transmitter of norepinephrine, improves contractility in mesenteric arteries of pre-hepatic portal hypertensive rats. Therefore, we investigated the effect of NPY on mesenteric arterial contractility in vitro and in vivo in cirrhotic ascitic rats, as well as the vasoactive pathways involved. METHODS: All experiments were performed in CCl₄-induced cirrhotic rats with ascites and compared to controls. In vivo haemodynamic characterisation was assessed before and after cumulative application of NPY i.v. using the microspheres technique. In vitro mesenteric arterial perfusion was used to analyse the effect of NPY on the response to α₁-adrenergic, as well as nitrergic stimulation. The NPY effects on vasoactive pathways (RhoA/Rho-kinase and NOS/NO) were analysed by western blot in mesenteric arteries. RESULTS: NPY decreased portal-venous blood flow and reduced portal pressure in cirrhotic rats, without changes in mean arterial pressure. This was accompanied by decreased cardiac output and normalised systemic vascular resistance in cirrhotic rats. By contrast, no significant splanchnic or systemic haemodynamic effect of NPY was seen in controls. NPY enhanced arterial contractility in cirrhotic but not in control rats. Furthermore, NO-mediated vasodilation was reduced to a greater extent than in controls. These findings were paralleled by an increased expression and activity of the constrictive Rho-kinase pathway and decreased activation of vasodilating NOS/NO signalling after NPY administration in mesenteric arteries. CONCLUSIONS: NPY exerts marked portal hypotensive effects and ameliorates the hyperdynamic circulation in cirrhotic ascitic rats. This is mediated mainly by a pronounced splanchnic vasoconstriction and reduction in splanchnic blood flow due to enhanced Rho-kinase expression and activity, as well as reduced NOS activation and NO effect. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/21317421/Amelioration_of_portal_hypertension_and_the_hyperdynamic_circulatory_syndrome_in_cirrhotic_rats_by_neuropeptide_Y_via_pronounced_splanchnic_vasoaction_ L2 - https://gut.bmj.com/lookup/pmidlookup?view=long&pmid=21317421 DB - PRIME DP - Unbound Medicine ER -