Cirrhotic portal hypertension: From pathophysiology to novel therapeutics

Figure 5 Portal pressure responses with Mas receptor and Mas-related G protein-coupled receptor type-D blockade and plasma angiotensin-(1-7) peptide (or blocker) concentrations.  A and B: Portal pressure responses after systemic administration of a bolus dose of Mas receptor (MasR) blocker D-Ala⁷-Ang-(1-7) (A779) (10 mg/kg) or Mas-related G protein-coupled receptor type-D (MrgD) blocker D-Pro⁷-Ang-(1-7) (D-Pro) (10 mg/kg) in cirrhotic carbon tetrachloride-induced (A) and bile duct ligated (B) rats. Both MrgD and MasR blockade significantly reduced portal pressure likely by blocking angiotensin-(1-7) [Ang-(1-7)] mediated splanchnic vasodilatation; C: Plasma concentrations of Ang-(1-7) peptide and blockers measured before and after a bolus intra-jugular injection of Ang-(1-7) peptide (3.5 mg), MasR blocker A779 (3.5 mg) or MrgD blocker D-Pro (3.5 mg). The peptide and the blockers were injected into healthy rats and plasma levels of Ang-(1-7) peptide were measured by a radioimmunoassay using an antibody directed at middle amino acids of the peptide. Each time point represents the mean ± SEM profile from 4 rats per treatment group. P < 0.001, baseline vs 2-min post-injection and 2-min vs 5-min post-injection. Adapted from reference[23]. CCl₄: Carbon tetrachloride-induced; BDL: Bile duct ligated; A779: D-Ala⁷-Ang-(1-7); D-Pro: D-Pro⁷-Ang-(1-7); Ang-(1-7): Angiotensin-(1-7).