9, 10 Although the effect of albumin on cardiac output is simply BGB324 mw attributed, in current opinion, to its ability to increase cardiac preload, the action of albumin in this situation can be far more complex. First, albumin binds many substances such as NO, reactive oxygen species
(ROS), and proinflammatory cytokines,11-14 which may be involved in the pathogenesis of both the peripheral arterial vasodilatation and the cardiac dysfunction in cirrhosis and ascites. In addition, it can be hypothesized that in cirrhosis, as in sepsis, albumin can exert a positive inotropic effect in the cardiac tissue through an inhibitory effect on the expression and activity of iNOS.15 The aim of our study was to verify in an animal model of cirrhosis with ascites if albumin infusion can improve cardiac contractility through a mechanism that is independent of the increase of the preload, and to define its possible molecular basis. Adcy3, adenylate cyclase
3; β-AR, beta-adrenergic receptor; BDL, bile duct-ligated; BSA, bovine serum albumin; CCl4, carbon tetrachloride; DTT, dithiothreitol; Idasanutlin molecular weight EGTA, ethylene glycol tetraacetic acid; ELISA, enzyme-linked immunosorbent assay; Gαi2, Gαi2 protein; Gαs, Gαs protein; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HES, hydroxyethyl starch; HPRT, hypoxanthine guanine phosphoribosyl transferase; HRS, hepatorenal syndrome; iNOS, inducible nitric oxide synthase; LVDP, left ventricular developed pressure; NAD(P)H, nicotinamide adenine dinucleotide phosphate; NF-κB, nuclear factor-κB; NO, nitric oxide; PKA, protein kinase A; PMSF, phenylmethylsulfonylfluoride; PRA, plasma renin activity; ROS, reactive oxygen species; SBP, spontaneous bacterial peritonitis; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TNF-α, tumor necrosis factor α. The study was performed in conscious, male, adult Wistar-Kyoto rats with cirrhosis and ascites, and in 上海皓元 conscious, male, adult Wistar-Kyoto control rats. The study was conducted in accordance with the principles and procedures outlined
in the National Institutes of Health Guide for the Care and Use of Laboratory Animals and was approved by the Italian Ministry of Health (approval on September 8th 2006 by the Italian Ministry of Health according to legislative decree no. 116/92). Cirrhosis was induced in adult (200-225 g) male Wistar-Kyoto rats (Charles River, Calco, Italy) by exposing the animals to the inhalation of carbon tetrachloride (CCl4) twice a week up to ascites appearance, as described.16 Thirty rats with cirrhosis and ascites and 30 control rats were housed in environmentally controlled facilities and allowed free access to chow and distilled water containing phenobarbital (Luminal 0.3 g/L, Bracco, Milan, Italy).