Liver, Pancreas, and Biliary TractRole of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension☆,☆☆
Section snippets
Animals
Male Sprague–Dawley rats (Charles River Laboratories, Saint-Aubin-Lès-Elbeuf, France) were divided into 2 groups. One group included 49 rats that underwent portal vein stenosis to induce portal hypertension, as described previously.10 Portal hypertension was considered to be present 14 days after surgery in portal vein–stenosed rats. A second group included 40 rats that underwent sham operations (sham-operated group) under pentobarbital anesthesia. Studies were performed in rats weighing
Results
Concentration-response curves were significantly lower in aortas from untreated portal hypertensive rats than in those from untreated sham-operated rats (Figure 1).After propranolol or atenolol administration in portal hypertensive rats, aortic concentration-response curves were significantly
Discussion
Evidence of increased NO production has been found in several models of portal hypertension with or without cirrhosis.3, 4 In these models, in vitro hyporeactivity to vasoconstrictors has been shown in aortas and the superior mesenteric artery from cirrhotic and portal vein–stenosed rats and was abolished by NO inhibition.2 These results suggest that NO overproduction is a major factor of systemic arterial vasodilation in portal hypertension. An increase in cytokines and endotoxin has been
Acknowledgements
The authors thank Dr. Fabienne Pessione and Dr. J. Paries for expert statistic advice and L. Font and A. Truskolasky for expert technical assistance.
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Address requests for reprints to: Didier Lebrec, M.D., INSERM Unité 481, Hôpital Beaujon, 92118 Clichy, France. e-mail: [email protected]; fax: (33) 1-47-30-17-11.
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Supported in part by Ferring SA France; Fondation pour la Recherche Médicale (to D.P.); and the Fondation Nationale Alfred Kastler and Ernst und Berta Grimmke-Stiftung (to J.H.).