The effects of hepatic steatosis on thromboxane A2 induced portal hypertension

Abstract Introduction and aim Thromboxane (TX) A 2 was identified as an important vasoconstrictor during Zymosan induced portal perfusion pressure (PP) increase. We aimed at investigating whether hepatic steatosis influences the extent of TXA 2 -induced portal hypertension. Materials and methods Sprague–Dawley rats were randomly divided into control and steatosis (induced by the special diet) groups. PP and TXB 2 (stable degradation product of TXA 2 ) in the perfusate were measured after in situ liver perfusion with Zymosan (150 μg/ml, 40–46 min) or U46619 (TXA 2 analog, 0.1 μM/ml, 40–46 min). The number of Kupffer cell (KC) was measured by immunohistochemistry with CD163. Results Zymosan induced more TXB 2 production and a higher PP increase in control group than in steatosis group despite more CD163 positive KCs in fatty livers. PP and TXB 2 efflux revealed a strong correlation in control group and a moderate correlation in steatosis group. Contrary to the effect of Zymosan, U46619 induced a much higher PP increase in steatosis group than in control group. Conclusion Severe steatosis increased number of KCs, however, PP increase and TXB 2 efflux caused by Zymosan infusion in fatty livers were lower than those in healthy livers. In contrast, TXA 2 analog caused higher PP increase in fatty livers. Targeting the more sensitive response to TXA 2 in fatty livers might be a potential therapy of severe steatosis.