Murine study of portal hypertension associated endothelin-1 hypo-response

Figure 3 Endothelin-1 hypo-response develops in wild type, iNOS^-/- and eNOS^-/- mice following portal vein ligation. A: Aortic blood flow was monitored in unadulterated wild type (squares), iNOS^-/- (diamonds) and eNOS^-/- (triangle) mice prior to and following IV administration of 5 pmol/kg endothelin-1 (ET1). ET1 induced a rapid vessel contraction and subsequent reduction in flow. Response to ET1 was significantly greater in eNOS^-/- when compared to wild type controls; B: Wild type, iNOS^-/- and eNOS^-/- mice were subjected to sham (open bars) or portal vein ligation surgery (PVL) (shaded bars). After 7 d changes in aortic flow was recorded following IV administration of 5 pmol/kg ET1. In all mouse groups the response to ET1 was markedly reduced following PVL (iNOS > wild type > eNOS^-/-); C: ET1 induced contraction of isolated aortic segments from unadulterated wild type (triangle) iNOS^-/- (square) and eNOS^-/- (triangle) mice were determined using an ADI 610M small animal myograph. Aortic vessel segments contracted to exogenous ET1. At high ET1 dose (10^-4 mol/L) aortic vessel segments from eNOS^-/- mice contracted significantly greater then segments from wild type controls; D: Wild type, iNOS^-/- and eNOS^-/- mice were subjected to sham (open bars) or portal vein ligation surgery (shaded bars). After 7 d the aorta was carefully dissected and ET1 contractility was measured. Ex-vivo aorta ET1 (10^-4 mol/L) contractility was significantly decreased in vessels from 7 d wild type, iNOS^-/- and eNOS^-/- PVL mice when compared to shams (PVL vs sham, P < 0.01).