ACTH-induced corticosterone changes in PVL rats without- (H(-), n = 21) or with-hemorrhage (H(+), n = 19).

<p>There was no significant difference (P>0.05).</p

Body weight and baseline hemodynamics in different groups.

<p>MAP: mean arterial pressure; PP: portal pressure; HR: heart rate;</p><p>PAHN: without hemorrhage; PAHV, PAHD3, PAHD5: hemorrhage groups treated with vehicle, dexamethasone 3 mg/kg, or 5 mg/kg, respectively.</p><p>P>0.05 between ACTH H (−) and H (+) groups, among PHN, PHV, PHD groups, and among PAHN, PAHV, PAHD3, PAHD5 groups.</p

Glypressin-induced hemodynamic changes in adrenalectomized PVL rats.

<p>(A) Chronological MAP changes in adrenalectomized PVL rats without-(PAHN, n = 7) or with-hemorrhage treated with vehicle (PAHV, n = 9), dexamethasone 3 (PAHD3, n = 7), or 5 mg/kg (PAHD5, n = 11). PAHD5 group had higher MAP2 than PAHD3 group and higher MAP3 than all groups (P<0.05); (B) PAHD5 group had higher MAP change (P<0.05 vs. all groups). (C) Chronological changes of PP. PAHN group had higher PP2 (P<0.05 vs. PAHD3 or PAHD5) and PAHD5 group had lower PP3 (P<0.05 vs. PAHV); (D) PAHN group had more prominent PP reduction (P<0.05 vs. PAHV or PAHD3).</p

Experimental design.

<p>G: glypressin; DW: distilled water (vehicle); Dexa: dexamethasone (3 or 5 mg/kg).</p

The vascular NOS mRNA expressions in PVL rats.

<p>AA: abdominal aorta; SMA: superior mesenteric artery; iNOS: inducible nitric oxide synthase; eNOS: endothelial NOS. PHV group had higher AA and SMA iNOS, eNOS expressions (P<0.05 vs. PHN), which were down-regulated by dexamethasone in AA (P<0.05 vs. PHD), but not in SMA.</p

TNF-α concentrations in (A) PVL (PHN, PHV, PHD) and (B) adrenalectomized PVL (PAHV, PAHV, PAHD3, PAHD5) groups.

<p>(A): TNF-α level was significantly higher in PHV group (P<0.05 vs. PHN) and was reduced by dexamethasone (P<0.05 PHV vs. PHD). (B): PAHV group had significantly higher TNF-α level (P<0.05 vs. all groups).</p

The vascular NOS mRNA expressions in adrenalectomized PVL rats.

<p>PAHV group had higher AA iNOS, eNOS expressions (P<0.001 vs. PAHN), in which iNOS was down-regulated by dexamethasone, especially 5 mg/kg (P<0.05, PAHD5 vs. PAHD3). PAHV group had higher SMA iNOS expression (P<0.001 vs. PAHN), which was down-regulated by dexamethasone, especially 5 mg/kg. PAHV group had higher SMA eNOS expression (P<0.05 vs. PAHN), which was down-regulated by dexamethasone (P<0.05 vs. PAHD3 or PAHD5).</p

Pulmonary and hepatic histology of CBDL rats with or without indomethacin treatment.

<p>The representative pulmonary H&E staining showed prominant polymorphonuclear cells accumulation with tissue necrosis and disruption of normal alveoli (magnification 200x). The infiltrative cells were reduced by indomethacin. Hepatic H&E staining revealed tissue necrosis and bile ductule proliferation, which were not influenced by indomethacin (magnification 200x). Hepatic Sirius Red staining revealed collagen fiber deposition (red in color), which was ameliorated by indomethacin (magnification 40x).</p

Selective cyclooxygenase inhibition by SC-560 improves hepatopulmonary syndrome in cirrhotic rats

<div><p>Objective</p><p>Hepatopulmonary syndrome (HPS) is characterized by hypoxia in patients with chronic liver disease. The mechanism of HPS includes pulmonary vasodilatation, inflammation, and angiogenesis. Prostaglandins synthesized by cyclooxygenases (COX) participate in vascular responsiveness, inflammation and angiogenesis, which can be modulated by COX inhibitors. We therefore evaluated the impact of COX inhibition in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS.</p><p>Methods</p><p>Cirrhotic rats were randomly allocated to receive non-selective COX inhibitor (indomethacin), selective COX-1 inhibitor (SC-560), or COX-2 inhibitor (celecoxib) for 14 days. After that, hemodynamic parameters, severity of hypoxia and intrapulmonary shunts, liver and renal biochemistry parameters, histological finding and protein expressions were evaluated.</p><p>Results</p><p>Non-selective COX inhibition by indomethacin improved hepatic fibrosis and pulmonary inflammation in cirrhotic rats with HPS. It also decreased mean arterial blood pressure, portal pressure, and alleviated hypoxia and intrapulmonary shunts. However, indomethacin increased mortality rate. In contrast, selective COX inhibitors neither affected hemodynamics nor increased mortality rate. Hypoxia was improved by SC-560 and celecoxib. In addition, SC-560 decreased intrapulmonary shunts, attenuated pulmonary inflammation and angiogenesis through down-regulating COX-, NFκB- and VEGF-mediated pathways.</p><p>Conclusion</p><p>Selective COX-1 inhibitor ameliorated HPS by mitigating hypoxia and intrapulmonary shunts, which are related to anti-inflammation and anti-angiogenesis.</p></div

Hemodynamic, biochemistry parameters, intrapulmonary shunts and blood gas analysis of CBDL rats receiving indomethacin or vehicle (control) treatment.

<p>Hemodynamic, biochemistry parameters, intrapulmonary shunts and blood gas analysis of CBDL rats receiving indomethacin or vehicle (control) treatment.</p