Isoflurane pretreatment lowers portal venous resistance by increasing hepatic heme oxygenase activity in the rat liver in vivo

Abstract

The heme oxygenase (HO) system contributes to the maintenance of hepatic perfusion and integrity. It was the objective of this study to determine the influence of isoflurane (ISO) on hepatic HO-1 induction and its impact on hepatic hemodynamics. Rats were pretreated with or without ISO for 5h. After hemodynamic measurements by pressure-, laser doppler-, and ultrasound based techniques, the liver was harvested. HO-1 was analyzed by an HO activity assay, Northern- and Western blotting. ISO pretreatment induced hepatic HO-1 mRNA and protein resulting in an increase of HO activity. No effect on hsp-27, hsp-70 and hsp-90 mRNA could be observed. ISO lowered portal resistance. HO inhibition by tin protoporphyrine IX increased portal resistance in ISO pretreated animals up to control levels. This was associated with an increase in portal pressure and a reduction of portal flow. Microvascular flux was also impaired after HO blockade and ISO. However, hepatic arterial and systemic hemodynamics remained unchanged, indicating a specific effect within the portal vascular bed. ISO pretreatment induces hepatic HO-1 mRNA and protein followed by an increase in HO activity, thereby reducing portal resistance. These findings indicate a beneficial effect of ISO on hepatic hemodynamics in vivo.