Abstract | BACKGROUND: Angiogenesis is an important determinant of the pathophysiology of portal hypertension contributing to the formation of portosystemic collateral vessels and the hyperdynamic splanchnic circulation associated to this syndrome. Somatostatin and its analogues, like octreotide, have been shown to be powerful inhibitors of experimental angiogenesis. AIM: To determine whether octreotide has angioinhibitory effects in portal hypertensive rats. METHODS: Partial portal vein-ligated (PPVL) rats were treated with octreotide or vehicle during 4 or 7 days. Splanchnic neovascularization and VEGF expression were determined by histological analysis and western blotting. Expression of the somatostatin receptor subtype 2 (SSTR2), which mediates the anti-angiogenic effects of octreotide, was also analyzed. Formation of portosystemic collaterals (radioactive microspheres) and hemodynamic parameters were also measured. RESULTS:
Octreotide treatment during 4 days markedly and significantly decreased splanchnic neovascularization, VEGF expression by 63% and portal pressure by 15%, whereas portosystemic collateralization and splanchnic blood flow were not modified. After 1 week of octreotide injection, portal pressure was reduced by 20%, but inhibition of angiogenesis escaped from octreotide therapy, a phenomenon that could be related to the finding that expression of SSTR2 receptor decreased progressively (up to 78% reduction) during the evolution of portal hypertension. CONCLUSION:
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Authors | Marc Mejias, Ester Garcia-Pras, Carolina Tiani, Jaime Bosch, Mercedes Fernandez |
Journal | Journal of cellular and molecular medicine
(J Cell Mol Med)
2008 Sep-Oct
Vol. 12
Issue 5A
Pg. 1690-9
ISSN: 1582-1838 [Print] England |
PMID | 18194463
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, Somatostatin
- Sstr2 protein, rat
- Vascular Endothelial Growth Factor A
- Somatostatin
- Nitric Oxide Synthase Type III
- Nos3 protein, rat
- Heme Oxygenase-1
- Octreotide
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Topics |
- Animals
- Gene Expression Regulation
(drug effects)
- Heme Oxygenase-1
(genetics, metabolism)
- Hemodynamics
(drug effects)
- Hypertension, Portal
(drug therapy, genetics, metabolism, pathology)
- Male
- Neovascularization, Pathologic
(drug therapy, genetics, metabolism)
- Nitric Oxide Synthase Type III
(genetics, metabolism)
- Octreotide
(chemistry, therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Receptors, Somatostatin
(metabolism)
- Somatostatin
(analogs & derivatives)
- Vascular Endothelial Growth Factor A
(genetics, metabolism)
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