Positive cardiac inotropic effect of albumin infusion in rodents with cirrhosis and ascites: molecular mechanisms.
The aim of this study was to evaluate the effect and molecular mechanism of albumin infusion on cardiac contractility in experimental cirrhosis with ascites. Cardiac contractility was recorded ex vivo in rats with cirrhosis and ascites and in control rats after the injection in the caudal vein of albumin, saline, or hydroxyethyl starch (HES). Gene and protein expression of β-receptors and pathways involved in their intracellular signaling such as Gα(i2) protein (Gα(i2)), adenylate cyclase 3 (Adcy3), protein expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS), were evaluated in cardiac tissue in both groups. Phosphorylation and membrane-translocation of the cytosolic components of nicotinamide adenine dinucleotide phosphate (NAD(P)H)-oxidase and translocation of nuclear factor kappa B (NF-κB) were also evaluated. After saline intravenous injection, cardiac contractility was significantly reduced in rats with cirrhosis as compared to control rats (P < 0.01). This was associated with: (1) increased expression of protein Gα(i2) (P < 0.05), TNF-α (P < 0.05), iNOS (P < 0.05); (2) increased NAD(P)H-oxidase activity (P < 0.05); (3) increased nuclear translocation of NF-κB (P < 0.05); and (4) lower expression of Adcy 3 (P < 0.05) in cardiac tissue of rats with cirrhosis. After albumin injection cardiac contractility (P < 0.01), protein expression of TNF-α, iNOS, Gα(i2), and Adcy3, NAD(P)H-oxidase activity and nuclear translocation of NF-κB in cardiac tissue of rats with cirrhosis were reversed to control levels (P < 0.05). HES injection did not modify cardiac contractility and nuclear translocation of NF-κB in cardiac tissue of rats with cirrhosis.


CONCLUSIONS
Albumin exerts a positive cardiac inotropic effect in rats with cirrhosis and ascites counteracting the negative effects of oxidative stress- and TNF-α-induced activation of NF-κB-iNOS pathway and oxidative stress-induced alteration of β-receptor signaling.
Department of Medicine DIMED, University of Padova Medical School, Italy.
Alessia
A
Bortoluzzi
Giulio
G
Ceolotto
Elisabetta
E
Gola
Antonietta
A
Sticca
Sergio
S
Bova
Filippo
F
Morando
Salvatore
S
Piano
Silvano
S
Fasolato
Silvia
S
Rosi
Angelo
A
Gatta
Paolo
P
Angeli
D000320:Adrenergic Fibers / Q000187:drug effects; D000418:Albumins / Q000008:administration & dosage*; D000818:Animals; D001201:Ascites / Q000188:drug therapy* / Q000209:etiology; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives; D007262:Infusions, Intravenous; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000418:Albumins; D002316:Cardiotonic Agents; D006895:Hydroxyethyl Starch Derivatives; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat