Abstract
The aim of this study is to elucidate the effects of different dosages of octreotide on portal pressure in cirrhotic patients and to investigate the mechanism of activated human hepatic stellate cells (HSCs) on octreotide. Thirty-one (31) hepatitis B-related cirrhotic patients were randomly assigned to receive treatment with a 50 (group A, n = 12) or a 25 µg/h infusion of octreotide for 72 h (group B, n = 14); the control group C (n = 5) received conventional treatment. Dynamic portal pressure was directly measured via a portal vein catheter. To study the cellular mechanism of octreotide, the expression of SSTRs 1-5 in LX-2, an HSC line, was examined by immunostaining and RT-PCR. Intracellular Ca2+ in LX2 was measured by laser scanning confocal microscopy (LSCM). The protein and mRNA levels in all five subtypes of SSTRs were positively expressed in LX-2. Octreotide led to an immediate two-fold drop in intracellular Ca2+ (P < 0.01). Portal pressure, in both groups A and B, decreased significantly (mean, - 20.6%) after octreotide infusion. Octreotide decreased portal pressure in cirrhotic patients by inhibiting HSC contractility by decreasing intracellular Ca2+ concentration via stimulation of all SSTRs on HSCs. Key words: Hepatic stellate cell, somatostatin receptor subtype, octreotide, portal hypertension, liver cirrhosis.
Highlights
Chronic liver diseases, especially liver cirrhosis, are often complicated with portal hypertension, which is characterized by increased intrahepatic vascular resistance and hyperdynamic states (Blei, 2007; Sanyal et al, 2008)
Immunocytochemical staining showed that LX-2 cells were positive for SSTR2 and SSTR5, which were mainly localized on the cell membrane and in the cytoplasm (Figure 1)
We showed that octreotide did not inhibit the up-regulation of intracellular Ca2+ concentration stimulated by KCl or ET-1
Summary
Especially liver cirrhosis, are often complicated with portal hypertension, which is characterized by increased intrahepatic vascular resistance and hyperdynamic states (Blei, 2007; Sanyal et al, 2008). Complications associated with portal hypertension occurs when the portal pressure exceeds. The most frequent and severe complication of portal hypertension, gastro-esophageal varices bleeding (EVB), has a high mortality rate in patients with cirrhosis (Dragoteanu et al, 2008; Garcia-Tsao, 2003). It is assumed that sustained reduction in portal pressure by long-term drug administration may prevent and treat the complications of portal hypertension (Garcia-Tsao et al, 2008; Minor and Grace, 2006). A major focus of management of patients with portal hypertension is to reduce functional portal venous flow and portal pressure
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