THE GUANYLATE CYCLASE-COUPLED NATRIURETIC PEPTIDE RECEPTOR - A NEW TARGET FOR PREVENTION OF COLD ISCHEMIA-REPERFUSION DAMAGE OF THE RAT-LIVER

Citation
Al. Gerbes et al., THE GUANYLATE CYCLASE-COUPLED NATRIURETIC PEPTIDE RECEPTOR - A NEW TARGET FOR PREVENTION OF COLD ISCHEMIA-REPERFUSION DAMAGE OF THE RAT-LIVER, Hepatology, 28(5), 1998, pp. 1309-1317
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
ISSN journal
0270-9139
Volume
28
Issue
5
Year of publication
1998
Pages
1309 - 1317
Database
ISI
SICI code
0270-9139(1998)28:5<1309:TGCNPR>2.0.ZU;2-1
Abstract
The aim of our studies was to investigate hormonal prevention of hepat ic preservation damage by the atrial natriuretic peptide (ANP) and the mechanisms involved. Isolated perfusion of rat livers was performed i n a nonrecirculating fashion. Twenty minutes of preischemic perfusion was performed with or without different concentrations of ANP, followe d by 24-hour storage in cold University of Wisconsin (UW) solution. Tw o hundred nanomoles of ANP prevented hepatocellular damage during a 2- hour reperfusion period as indicated by a marked attenuation of the si nusoidal efflux of lactate dehydrogenase (LDH) and purine nucleoside p hosphorylase (PNP), and by reduced Trypan blue uptake. Furthermore, po stischemic bile flow as an indicator of liver function was significant ly improved by about 60% with 200 nmol/L ANP, No protection was convey ed by 20 nmol/L ANP nor by pretreatment with 200 nmol/L ANP for only 1 0 minutes. The effects of ANP seemed to be mediated by the guanylate c yclase-coupled A (GC-A) receptor and cyclic guanosine monophosphate (c GMP), whereas expression of both GC-A and GC-B receptors as well as of the GC-C receptor was found, cGMP did protect from ischemia-reperfusi on damage, but selective ligands of the B and C receptor did not. To b egin to determine the mechanisms of ANP-mediated protection, different parameters were investigated: ANP had no effect on portal pressure as an indicator of hepatic circulation, nor on intracellular energy depl etion determined by adenosine nucleotide concentration. However, the m arked augmentation of nuclear factor kappa B (NF-kappa B) binding acti vity during reperfusion was prevented in ANP-pretreated livers. In con clusion, pretreatment with ANP protects the rat liver from cold ischem ia-reperfusion damage. This effect is mediated via the GC-A receptor a nd cGMP, and may be linked to an influence of ANP on NF-kappa B activa tion. Thus, ANP signaling via the GC-A receptor should be considered a s a new pharmacological target to prevent preservation injury of the l iver.