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Volume 124, Issue 5, Pages (May 2003)

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Presentation on theme: "Volume 124, Issue 5, Pages (May 2003)"— Presentation transcript:

1 Volume 124, Issue 5, Pages 1500-1508 (May 2003)
The role of nitric oxide synthase isoforms in extrahepatic portal hypertension: studies in gene-knockout mice  Nicholas G Theodorakis, Yi-ning Wang, Nicholas J Skill, Matthew A Metz, Paul A Cahill, Eileen M Redmond, James V Sitzmann  Gastroenterology  Volume 124, Issue 5, Pages (May 2003) DOI: /S (03)

2 Figure 1 Comparison of splenic pulp pressure and portal venous pressure in mice. Wild-type mice (n = 6) were anesthetized and laparotomized. The splenic pulp pressure and the Ppv were determined using a saline-filled manometer. ∗P < 0.05. Gastroenterology  , DOI: ( /S (03) )

3 Figure 2 Portosystemic shunt in portal vein-ligated mice. Wild-type mice were subjected to partial PVL or sham-operated as described in Materials and Methods. Fourteen days later, the mice were anesthetized and laparotomized. Fifteen micron red or blue fluorescent microspheres (approximately 105 each) were injected in the spleen (red spheres) or the femoral vein (blue spheres). The livers and lungs were harvested and the spheres extracted and visualized by fluorescence microscopy. Representative microscopic fields of microspheres isolated from the livers (A and C ) or the lungs (B and D) of sham (A and B) or portal vein-ligated (C and D) mice are shown. Gastroenterology  , DOI: ( /S (03) )

4 Figure 3 Elevation of splenic pulp pressure in portal vein-ligated mice. Wild-type mice were subjected to partial portal vein ligation (7–11 animals per time point) or sham operated (3–5 animals per time point) as described in Materials and Methods. At the indicated times, the mice were anesthetized, laparotomized, and the splenic pulp pressure (an index of Ppv) determined using a saline-filled manometer. ∗P < vs. unligated (sham) mice. Gastroenterology  , DOI: ( /S (03) )

5 Figure 4 Splenic pulp pressure in wild-type and gene-deficient mice after PVL. Wild-type or iNOS- or eNOS-deficient mice were sham operated or portal vein-ligated as described. Splenic pulp pressures (an index of Ppv) were measured 14 days later. (A ) Splenic pulp pressure in wild-type (B6, 129P) or iNOS (−/−) knockout mice after sham operation or after partial PVL. (B) Splenic pulp pressure in wild-type (C57BL.6J) or eNOS (−/−) knockout mice after sham operation or partial PVL. ∗P < 0.05 versus unligated mice. (C ) PCR products from wild-type (lanes 1, 3, 5, 7), iNOS knockout (lanes 2, 6), eNOS knockout (lanes 4, 8) mouse tail DNA after amplification using primers specific for the iNOS (lanes 1–4) or eNOS (lanes 5–8) gene. Lane 9 is a 100 base pair DNA ladder. The positions of the specific amplification products are indicated on the left with arrows. Gastroenterology  , DOI: ( /S (03) )

6 Figure 5 Serum NOx levels in wild-type and gene-deficient mice after PVL. Blood was collected by cardiac puncture from unligated (day 0) wild-type, iNOS (−/−), and eNOS (−/−) mice and 2, 4, and 14 days after PVL. Each group had 6 to 8 animals per time point. Total serum nitrate/nitrite was measured by the Greiss reaction after reduction of nitrate to nitrite. The results are expressed as the percent of the serum nitrate/nitrite levels in untreated mice. ∗P < 0.05 versus unligated (sham) mice. Gastroenterology  , DOI: ( /S (03) )

7 Figure 6 Abdominal aortic flow (Qao) in wild-type (WT) and gene-deficient mice after PVL. Wild-type or iNOS- or eNOS-deficient mice were sham operated (3 animals per time point) or portal vein ligated (6 animals per time point) as described. Fourteen days later the mice were anesthetized, laparotomized, and the abdominal aortic flow was measured using an ultrasonic flow probe. ∗P < 0.05 versus unligated (sham) mice. Gastroenterology  , DOI: ( /S (03) )

8 Figure 7 Portosystemic shunt in wild-type and gene-deficient mice after PVL. Wild-type or iNOS- or eNOS-deficient mice were sham operated or portal vein ligated as described (3 to 6 animals per time point). Fourteen days later the fluorescent microspheres were injected in the spleen as described. The number of spheres present in the lungs and livers was determined by fluorescence microscopy. The level of portosystemic shunt is calculated by the number of spheres present in the lungs divided by the number in the liver plus lungs, × 100. ∗P < versus unligated (sham) mice. Gastroenterology  , DOI: ( /S (03) )


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