angiotensinogen and Hypertension--Portal

To investigate the expression of local angiotensinogen mRNA and activation of local nuclear factor-kappaB in vasculopathy of portal hypertension and to discuss their role in the pathogenesis of portal hypertensive vasculopathy.. RT-PCR was used to detect the expression of local angiotensinogen mRNA in 28 specimens of splenic artery and vein obtained during operation of elective separation and amputation on 28 portal hypertension (PH) patients, 20 males and 8 females, aged 51.7 +/- 10 (30 - 65), and in 12 specimens of normal vessel from 12 patients undergoing splenectomy due to traumatic rupture of spleen. Chemiluminescent electrophoretic mobility shift assay (EMSA) was used to detect the activation of NF-kappaB in splenic artery and vein.. The levels of local angiotensinogen mRNA in the splenic artery and vein of PH group were 0.48 +/- 0.21 and 0.43 +/- 0.16 respectively, both significantly higher than those in the control group (0.23 +/- 0.12 and 0.18 +/- 0.10, both P < 0.05). There was no significant difference between the splenic artery and vein in the expression of local angiotensinogen mRNA in PH group. The activation levels of NF-kappaB in splenic artery and vein of the PH patients were 1.44 +/- 0.23 and 1.38 +/- 0.18 respectively, both significantly higher than those of the control group (0.19 +/- 0.20 and 0.25 +/- 0.16 respectively, both P < 0.05). However, there was no significant difference in the activation levels of NF-kappaB between the splenic artery and vein in the PH patients (P > 0.05).. Local angiotensinogen and activation of NF-kappaB maybe one of the factors in the pathogenesis of portal hypertensive vasculopathy, which can cause and advance portal hypertensive vasculopathy.

Topics: Adult; Aged; Angiotensinogen; Female; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; NF-kappa B; RNA, Messenger; Splenic Artery; Splenic Vein

To investigate the expression of local renin and angiotensinogen mRNA in cirrhotic portal hypertensive patients.. The expression of local renin and angiotensinogen mRNA in the liver, splenic artery and vein of PH patients was detected by RT-PCR analysis.. Expression of local renin mRNA in the liver of control group was (0.19+/-0.11), significantly lower than that in splenic artery (0.45+/-0.17) or splenic vein(0.39+/-0.12) respectively, (P<0.05). Expression of local angiotensinogen mRNA in the liver was (0.64+/-0.21), significantly higher than that in splenic artery(0.41+/-0.15) or in splenic vein (0.35+/-0.18) respectively, (P<0.05). Expression of local renin mRNA in the liver, splenic artery and vein of PH group was (0.78+/-0.28), (0.86+/-0.35) and (0.81+/-0.22) respectively, significantly higher than that in the control group, (P<0.05). Expression of local angiotensinogen mRNA in the liver, splenic artery and vein of PH group was (0.96+/-0.25), (0.83+/-0.18) and (0.79+/-0.23) respectively, significantly higher than that in the control group, (P<0.05). There was no significant difference between the liver, splenic artery and vein in the expression of local renin or local angiotensinogen mRNA in PH group, (P<0.05).. In normal subjects the expression of local renin and angiotensinogen mRNA was organ specific, but with increase of the expression of LRAS, the organ-specificity became lost in cirrhotic patients. LRAS may contribute to increased resistance of portal vein with liver and formation of splanchnic vasculopathy.

Topics: Adult; Aged; Angiotensinogen; Endothelium, Vascular; Female; Gene Expression; Humans; Hypertension, Portal; Immunohistochemistry; Liver Cirrhosis; Male; Microscopy, Electron, Scanning; Middle Aged; Organ Specificity; Renin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Splenic Vein

Activation of antinatriuretic systems such as the renin-angiotensin system, is of major importance in the pathogenesis of sodium retention in cirrhosis. In this study, we studied the intrarenal renin-angiotensin system by measuring renin and angiotensinogen mRNA expression in the kidney of rats subjected to long-term bile duct ligation in a phase before the development of ascites, when sodium retention is already present. Experiments were performed in sham-operated and bile duct-ligated rats 3 wk after surgery. Balance studies showed lower sodium excretion and greater sodium retention in the bile duct-ligated rats compared with the control animals. Plasma renin activity (4.41 +/- 1.01 ng Angiotensin I/ml/hr in the bile duct-ligated group vs. 4.20 +/- 0.74 in the controls) and plasma renin concentration were not different between the two groups. However, plasma renin substrate was significantly decreased in bile duct-ligated animals. Total kidney renin mRNA was significantly higher in the bile duct-ligated animals (0.83 +/- 0.14 densitometric units vs. 0.44 +/- 0.04 in the controls), as determined on Northern-blot analysis and densitometric quantitation. Angiotensinogen mRNA expression in the kidneys of bile duct-ligated rats was significantly decreased (0.09 +/- 0.01 densitometric units) compared with that of the controls (0.21 +/- 0.03). These results indicate that sodium-retaining, nonascitic bile duct-ligated rats show abnormalities of the intrarenal renin angiotensin system that precede changes in plasma renin activity. Our data suggest that the intrarenal renin angiotensin system may participate in the initiation of the renal pathophysiological abnormalities present in bile duct-ligated rats.

Topics: Angiotensinogen; Animals; Bile Ducts; Disease Models, Animal; Gene Expression; Hypertension, Portal; Kidney; Ligation; Liver Cirrhosis, Experimental; Male; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger