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P-331 Increased production of nitric oxide and its role in the portal circulation in cirrhotic rats
Posters/International Hepatology Communications 3 Suppl. (1995) $37-$169
P.329
CI-L~NGE IN PLASI~L¢ CONCENTRATION OF BINDING FREE CATECHOL.~IINES IN THE PORTAL CIRCULATION FOLLOWING THE PORTAL LIGATION IN RAT B.Kawai. A.Ohnishl. T.Ohno. A.Matsuo. T.Inoue. T.Tanaka Dept.lnternal Medieinefl). Daisan Hosp. The Jikei Univ. School Medicine. Tokyo. Japan To investigate the role of eateeholamines (CA) in increased portal pressure following the portal vein ligation, we measured free plasma CA (norepinephrine'NE. epinephrine:E) concentrations serially for five hours (in :30 minutes interval) in 26 portal vein hgated rats and 5 sham-operated rats, using mierodialysis system. We employed the mierodialysis technique in conjunction with highperfolTnanee hquid chromatography, since being measurable for only small amount sample (10 #1) to obtain plasma CA levels. A coaxial mierodiab'sls probe covered by a dialyzing membrane :3.0 mm in length and 0.5 mm in diameter was inserted into the portal vein at the post ligated site. A ligature of 3.0 silk was tied around the portal vein with a metal needle 1.2 mm i.d. and then the needle was removed. Binding-free NE increased almost twice to 15.9+1.8 (mean = SEM) pg/60 tt 1 /:30 min 0.5 hour after (P<0.05), and thereafter increased more triplicate to 3 0 . I - 5 . 5 (P<0.01) 5 hours after ligation from 9.6 =2.1 of the preligation baseline value. Binding-free E increased, in same manner to NE. triplicate to 23.1 + 11.3 significantly 5 hours after hgation from 7.4± 1.5 of the preligation value. We did not observed any significant increases in these plasma levels from those of ligated animals in sham-operated rats. The results suggested that postligated increase in portal pressure and/or progress m eolateral circulation could be related to the endogenously enhanced eateeholamines and increased hepatol~ortal sympathetic nervous activity.
O'1"11
S 119
P-330
NATRIURESIS AND SYSTEMIC HEMODYNAMIC EFFECTS OF BRAIN NATRIURETIC R E P T I D E ( B N P ) I N RATS W I T H C I R R H O S I S H . K o m e i c h i , M . O o s u g a , H.Terada, K.Satomura, Y.Katsuta, T . A r a m a k i D, R . M o r e a u , D . L e b r e c 2) 1st D e p a r t m e n t o f Internal Medicine, Nippon Medical School 1~, I N S E R M U-24 Hopital Beaujon ~-)
The effects of brain natriuretic peptide (BNP) on renal excretion o f sodium, and systemic and regional h e m o d y n a m i c s have not yet been studied in cirrhosis. Thus, the effects o f BNP (300 and 600 n g / k g / m i n i.v.) were e x a m i n e d in normal and cirrhosis rats. In normal rats, natriuresis and diuresis were significantly higher with 600 ng dose o f BNP, respectively than with saline, while, in cirrhotic rats, the effects of BNP did not significantly differ from the effects of saline. Regional and systemic h e m o d y n a m i c s were not changed by BNP in normal rats. In cirrhotic rats, BNP significantly decreased portal tributary blood flow, portal pressure and cardiac index. In conclusion, the natriuretic response to pharmacological doses of BNP is blunted in rats with cirrhosis. This bhmting may be related to an activation of the endogenous antinatriuretic systems secondary to decreased cardiac index. Finally, BNP have a portal hypotensive action.
I st Dep of Surgery', Ky-oto umv. school of medicine. Kyoto,Japan606
P-332 RoLE OF THE SPLEEN IN THE REMNANT LIVER DYSFUNCFION AFTER EXTENSIVE HEPATECTOMY: WITH SPECIAL REFERENCE TO EXPRF-~SION OF ADHESION MOLECULES AND CHANGES IN NITRIC OXIDE LEVELS IN LIVER TISSUE M. K:itngawa,H. Sakurai, T. Noguehi, Y. 1st Dept. of Surgery, Mie Univ. School of Medicine, Tsu, Japan
The present study was aimed to clarify the significance of mtric oxide(NO) m the portal clrculatmn in cirrhosis.Using male Wistar rats. liver cirrhosis was induced by oral admmastratmn of CCl4.Rats were classified into ttnee groups: control.cirrhotic rats without ascltes arid with ascites.NO2NO3- as the stble metabohtes of NO were measured by Gr/ess reactlon. N~TA. inhibitor of NO synthesis.was administrated intravenously and portal pressure.portal blood flow were meastn~d.and pot'tsl venous resistance was calculated In addition.we measured the mtrnhepaticpressure of the ~solated hver perfused with KHBBS contaimng N~A.Furthermore,we measurad NO synthetic activity in the cultured hepatoc)xes.Kepffereells and slnusoidal endthelial ceils by the stimulation of L-m'ginine. Northern blotting was c~riedout to examine the expression of 1NOS-mRNA in the hver spleen.lung.and kidney.Results were as follow. Serum level of N O 2 - / N 0 3 - w a s higher In cirrhosis than in control. In the cirroht~c groups the portal blood flow was increased, and NNA reduced blood flow more than in the control groups.The increase of the portal venous resistance was more remarkable in cirrhosis The change of portal pressure by NNA was similiar among the three groups.The NO2:NO3- synthetac activity was higher in the hepatocytes from cirrhosis than that from control.The expression of iNOS-mRNA was high in the lung of the cirrhotic rats. In conclusion,this study suggested that in cirrhosis. vasorelaxation in the portal system was induced by NO. leading to the increase of the portal blood flow, and that increased serum level of NO in zarrhbsis was partly due to the enhanced synthesis by hepatocytes and lung.
We assessed the role of the spleen in the fiver dysfonedon following extensive hepetectomy based on relationships to nitric oxide (NO) changes and adhesion molecule expression. We divided adult mongrel dogs into two groups, 84%-hepateclomy group (Group I) and 84%-hepatectomy + splenectomy group (Group II), then serially memnm~ following parameters until 24 hours postoperatively : 1) AKBR, 2) blood hyaluronic aeld (HA) levels, 3) liver microcireulation, 4) liver tissue NO level (NO-Hb), and 5) ICAM-1 expression of liver. < R e s u l t s > AKBR levels became lower ~ a t e l y afteroperation and later recovered. However, while recovery of AKBR levels was good in Group II, in Group I, recovery was delayed. HA levels were elevated in both groups in-anediately after operation, but were significantly higher in Group I than in Group IL They were negatively cenelated with changes in liver tissue blood flow. Immediately after operation, liver tissue NO levels were significantly higher in both groups, but the changes occuned at significantly lower levels in Group lI than Group I. While expression of ICAM-1 in renmant liver tissue in Group It was observed only in the sinusoid, in Group I expression extend to hepetecytes, ~ ICAM-1 expression was particularly high in the animals which in which NO levels couldnot be maintained, and decreased. Liver tissue NO and ICAM-1 expression varied depending on the severity of the impairment of the sinusoidal endotefial cells, but both the changes in NO and expression of ICAM-1 were milder in the group which underwent combined splenectomy, suggesting that the spleen are involved in the remnant liver dysfunction in the early postoporaive period, particularlyin the progression of sinusoidal endothelial cell damage.
.t - o o . t I N C R E A S E D P R O D U C T I O N OF NITRIC O X I D E A N D ITS R O L E IN T H E P O R T A L CIRCLILATION IN CIRRHOTIC R A T S M A S A K I M I Z U M A T O , SHIGEKI ARII M A S A H A R U FURUTANI, TOSHIO N A K A M U R A , K A Z U N O B U M O N D E N , S A T O R U ISHIGURO, SHIN~'NICHI FUJITA, M A S A Y U K I I M A M U R A
P.329
CI-L~NGE IN PLASI~L¢ CONCENTRATION OF BINDING FREE CATECHOL.~IINES IN THE PORTAL CIRCULATION FOLLOWING THE PORTAL LIGATION IN RAT B.Kawai. A.Ohnishl. T.Ohno. A.Matsuo. T.Inoue. T.Tanaka Dept.lnternal Medieinefl). Daisan Hosp. The Jikei Univ. School Medicine. Tokyo. Japan To investigate the role of eateeholamines (CA) in increased portal pressure following the portal vein ligation, we measured free plasma CA (norepinephrine'NE. epinephrine:E) concentrations serially for five hours (in :30 minutes interval) in 26 portal vein hgated rats and 5 sham-operated rats, using mierodialysis system. We employed the mierodialysis technique in conjunction with highperfolTnanee hquid chromatography, since being measurable for only small amount sample (10 #1) to obtain plasma CA levels. A coaxial mierodiab'sls probe covered by a dialyzing membrane :3.0 mm in length and 0.5 mm in diameter was inserted into the portal vein at the post ligated site. A ligature of 3.0 silk was tied around the portal vein with a metal needle 1.2 mm i.d. and then the needle was removed. Binding-free NE increased almost twice to 15.9+1.8 (mean = SEM) pg/60 tt 1 /:30 min 0.5 hour after (P<0.05), and thereafter increased more triplicate to 3 0 . I - 5 . 5 (P<0.01) 5 hours after ligation from 9.6 =2.1 of the preligation baseline value. Binding-free E increased, in same manner to NE. triplicate to 23.1 + 11.3 significantly 5 hours after hgation from 7.4± 1.5 of the preligation value. We did not observed any significant increases in these plasma levels from those of ligated animals in sham-operated rats. The results suggested that postligated increase in portal pressure and/or progress m eolateral circulation could be related to the endogenously enhanced eateeholamines and increased hepatol~ortal sympathetic nervous activity.
O'1"11
S 119
P-330
NATRIURESIS AND SYSTEMIC HEMODYNAMIC EFFECTS OF BRAIN NATRIURETIC R E P T I D E ( B N P ) I N RATS W I T H C I R R H O S I S H . K o m e i c h i , M . O o s u g a , H.Terada, K.Satomura, Y.Katsuta, T . A r a m a k i D, R . M o r e a u , D . L e b r e c 2) 1st D e p a r t m e n t o f Internal Medicine, Nippon Medical School 1~, I N S E R M U-24 Hopital Beaujon ~-)
The effects of brain natriuretic peptide (BNP) on renal excretion o f sodium, and systemic and regional h e m o d y n a m i c s have not yet been studied in cirrhosis. Thus, the effects o f BNP (300 and 600 n g / k g / m i n i.v.) were e x a m i n e d in normal and cirrhosis rats. In normal rats, natriuresis and diuresis were significantly higher with 600 ng dose o f BNP, respectively than with saline, while, in cirrhotic rats, the effects of BNP did not significantly differ from the effects of saline. Regional and systemic h e m o d y n a m i c s were not changed by BNP in normal rats. In cirrhotic rats, BNP significantly decreased portal tributary blood flow, portal pressure and cardiac index. In conclusion, the natriuretic response to pharmacological doses of BNP is blunted in rats with cirrhosis. This bhmting may be related to an activation of the endogenous antinatriuretic systems secondary to decreased cardiac index. Finally, BNP have a portal hypotensive action.
I st Dep of Surgery', Ky-oto umv. school of medicine. Kyoto,Japan606
P-332 RoLE OF THE SPLEEN IN THE REMNANT LIVER DYSFUNCFION AFTER EXTENSIVE HEPATECTOMY: WITH SPECIAL REFERENCE TO EXPRF-~SION OF ADHESION MOLECULES AND CHANGES IN NITRIC OXIDE LEVELS IN LIVER TISSUE M. K:itngawa,H. Sakurai, T. Noguehi, Y. 1st Dept. of Surgery, Mie Univ. School of Medicine, Tsu, Japan
The present study was aimed to clarify the significance of mtric oxide(NO) m the portal clrculatmn in cirrhosis.Using male Wistar rats. liver cirrhosis was induced by oral admmastratmn of CCl4.Rats were classified into ttnee groups: control.cirrhotic rats without ascltes arid with ascites.NO2NO3- as the stble metabohtes of NO were measured by Gr/ess reactlon. N~TA. inhibitor of NO synthesis.was administrated intravenously and portal pressure.portal blood flow were meastn~d.and pot'tsl venous resistance was calculated In addition.we measured the mtrnhepaticpressure of the ~solated hver perfused with KHBBS contaimng N~A.Furthermore,we measurad NO synthetic activity in the cultured hepatoc)xes.Kepffereells and slnusoidal endthelial ceils by the stimulation of L-m'ginine. Northern blotting was c~riedout to examine the expression of 1NOS-mRNA in the hver spleen.lung.and kidney.Results were as follow. Serum level of N O 2 - / N 0 3 - w a s higher In cirrhosis than in control. In the cirroht~c groups the portal blood flow was increased, and NNA reduced blood flow more than in the control groups.The increase of the portal venous resistance was more remarkable in cirrhosis The change of portal pressure by NNA was similiar among the three groups.The NO2:NO3- synthetac activity was higher in the hepatocytes from cirrhosis than that from control.The expression of iNOS-mRNA was high in the lung of the cirrhotic rats. In conclusion,this study suggested that in cirrhosis. vasorelaxation in the portal system was induced by NO. leading to the increase of the portal blood flow, and that increased serum level of NO in zarrhbsis was partly due to the enhanced synthesis by hepatocytes and lung.
We assessed the role of the spleen in the fiver dysfonedon following extensive hepetectomy based on relationships to nitric oxide (NO) changes and adhesion molecule expression.
.t - o o . t I N C R E A S E D P R O D U C T I O N OF NITRIC O X I D E A N D ITS R O L E IN T H E P O R T A L CIRCLILATION IN CIRRHOTIC R A T S M A S A K I M I Z U M A T O , SHIGEKI ARII M A S A H A R U FURUTANI, TOSHIO N A K A M U R A , K A Z U N O B U M O N D E N , S A T O R U ISHIGURO, SHIN~'NICHI FUJITA, M A S A Y U K I I M A M U R A