Patterns of vasoregulatory gene expression in the liver response to ischemia/reperfusion and endotoxemia

• Published in: Shock (Augusta, Ga.) Ga.), 1999-03, Vol.11 (3), p.175-179
• Main Authors: SONIN, N. V, GARCIA-PAGAN, J.-C, NAKANISHI, K, ZHANG, J. X, CLEMENS, M. G
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Emergency and intensive care: infection, septic shock; Endothelin-1 - genetics; Endotoxemia - genetics; Gene Expression Regulation; Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase-1; Intensive care medicine; Ischemia - genetics; Lipopolysaccharides; Liver - blood supply; Liver - physiopathology; Male; Medical sciences; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin - genetics; Reperfusion; Reperfusion Injury
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/00024382-199903000-00004

Oxidative stress and inflammatory reactions associated with stresses that may lead to shock promote hepatic microcirculatory dysfunction, which may lead to hepatic injury. Because altered liver microcirculation may result from an imbalance in the expression of stress-induced vasoactive mediators, our study was conducted to investigate changes in the expression of genes encoding endothelin-1 (ET-1), its receptors, ET(A) and ET(B), heme-oxygenase 1 (HO-1), and inducible nitric oxide synthase (iNOS), using two different rat models of liver stress: ischemia/reperfusion of the liver and lipopolysaccharide (LPS)-induced endotoxemia. In ischemia/reperfusion experiments, rats were subjected to 1 h hepatic ischemia, followed by 6 h of reperfusion. Endotoxemia was induced by i.p. injection of LPS (1 mg/mL/kg body weight); rats were studied after 6 h. mRNA levels were estimated using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on total RNA samples prepared from experimental and sham control rat livers. In the ischemic reperfused livers the levels of mRNA for ET-1, ET(B), HO-1, and iNOS were significantly elevated. The fold increase versus sham was 2.5+/-1.1 (ET-1), 2.1+/-1.3 (ET(B)), 2.1+/-.8 (HO-1), and 6.4+/-3.9 (iNOS). In contrast, the expression of ET(A) receptor gene was reduced after ischemia/reperfusion (to 73+/-1% of sham). In the separate experiments we analyzed the same mRNAs levels after 1 h of ischemia (no reperfusion), and did not detect any changes. During endotoxemia we observed a marked increase in iNOS mRNA level (>24-fold), as well as a marked elevation of the other four mRNAs. The fold increase versus sham was 6.1+/-1.7, ET-1); 1.5+/-.3 (ET(A)); 1.6+/-.4 (ET(B)); and 2.4+/-.34 (HO-1). These results show that liver stress, induced by ischemia/reperfusion or LPS injection have characteristic patterns of vasoregulatory genes expression indicating that, although both stresses result in an increase in specific vascular reactivity, different pathways are involved in inducing the hepatic vascular stress response.