Relationship between angiotensin-(1-7) and angiotensin II correlates with hemodynamic changes in human liver cirrhosis

Abstract

AIM: To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system (RAS) components and hemodynamic changes. METHODS:Patients were allocated into 4 groups: mild-to-moderate liver disease (MLD), advanced liver disease (ALD), patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity (PRA), angiotensin (Ang) Ⅰ, Ang Ⅱ, and Ang-(1-7) levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components. RESULTS:PRA and angiotensins were elevated in ALD when compared to MLD and controls (P < 0.05). In contrast, Ang Ⅱ was significantly reduced in MLD. Ang-(1-7)/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-(1-7)/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation (0.52 ± 0.08 vs 0.38 ± 0.04, P < 0.02), whereas the peripheral circulating Ang Ⅱ/Ang Ⅰ ratio was elevated in comparison to splanchnic levels (0.18 ± 0.02 vs 0.13 ± 0.02, P < 0.04). Ang-(1-7)/ Ang Ⅱ ratios positively correlated with cardiac output (r = 0.66) and negatively correlated with systemic vascular resistance (r = -0.70). CONCLUSION:Our findings suggest that the relationship between Ang-(1-7) and Ang Ⅱ may play a role in the hemodynamic changes of human cirrhosis.

Is there a link between glucose levels and heart failure? An update

“…Ang-(1-7) has been associated to the physiopathology of several diseases such as hypertension, preeclampsia, hypertrophic myocardial disease and CHF, MI, chronic renal diseases, diabetic nephropathy, GDM and cirrhosis (62,63). Further studies should try to better elucidate the role of Ang- (1-7), as opposed to Ang II, in diabetes.…”

Role of Angiotensin Peptides Precursor in Ethanol Mediated Hepato toxicity: Perspective on Angiotensinogen

“…Nevertheless, the transgenic studies demonstrate that this polymorphism neither changes the expression of the AGT nor increases blood pressure [55]. In conclusion, inhibition of the RAS in experimental animals and clinical studies has proven effective in counteracting fibrosis, cirrhosis, and hypertension [6,13,14,16]. Thus the involvement of Ang II in fibrosis, cirrhosis and hypertension, puts the precursor AGT in a critical role.…”

“…In addition to classical pathways of production of Ang II, another homologue of ACE, ACE2 clips of one amino acid from carboxyl ends of Ang I to produce Ang 1-9 [13]. From Ang 1-9, Ang 1-7 is produced that possess opposite biological effects compared with Ang II [13][14][15][16]. Ang II can also be converted into Ang 1-7 by ACE2 [17,18].…”

“…Production of Ang 1-7 and its opposite biological effects as compared to Ang II constitutes another axis or alternate pathway of angiotensins action [16,19,20]. A schematic presentation of pathways for production of biologically active peptides from precursor AGT is depicted in Fig.…”

“…Production of Ang 1-7 provides neuroprotective, cardioprotective, and hepatoprotective effects [16,19,20]. ACE2 also serves as the receptor of severe acute respiratory syndrome [SARS] virus glycoprotein [21] .…”