ascorbic-acid and Hypertension--Portal

Patients with cirrhosis show intrahepatic endothelial dysfunction, characterized by an impaired flow-dependent vasorelaxation. This alteration is responsible for the marked postprandial increase in portal pressure and is attributed to an insufficient release of nitric oxide (NO). Ascorbic acid reverts endothelial dysfunction in other vascular disorders, via the increase of NO bioavailability through the neutralization of superoxide anions, thus preventing the scavenging of NO by superoxide. This study examined whether acute ascorbic acid administration might improve endothelial dysfunction in cirrhosis. Thirty-seven portal hypertensive patients with cirrhosis had measurements of hepatic and systemic hemodynamics, ascorbic acid, and malondialdehyde (MDA). Patients were randomly allocated to receive ascorbic acid (3 g, intravenously, n = 15) or placebo (n = 12) followed by a liquid meal. A third group received ascorbic acid followed by a sham meal (n = 10). Measurements were repeated after 30 minutes (hepatic venous pressure gradient at 15 and 30 minutes). Patients with cirrhosis had significantly lower ascorbic acid levels and higher MDA than healthy controls. Ascorbic acid significantly reduced MDA levels and markedly attenuated the postprandial increase in the hepatic venous pressure gradient (4% +/- 7% vs. 18% +/- 10% in placebo at 30 minutes, P < .001). Ascorbic acid followed by sham meal did not modify hepatic or systemic hemodynamics. In conclusion, patients with cirrhosis exhibited intrahepatic endothelial dysfunction, associated with decreased levels of ascorbic acid and increased levels of MDA. Ascorbic acid improved intrahepatic endothelial dysfunction, blunting the postprandial increase in portal pressure. These results encourage the performance of further studies testing antioxidants as adjunctive therapy in the treatment of portal hypertension.

Topics: Aged; Antioxidants; Ascorbic Acid; Double-Blind Method; Endothelium; Female; Hemodynamics; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Male; Malondialdehyde; Middle Aged; Nitric Oxide; Oxidative Stress; Postprandial Period; Splanchnic Circulation; Superoxides

In rats with chronic portal hypertension (PH) and common bile duct ligation (CBDL), significant ileal bacterial overgrowth, translocation of indigenous intestinal bacteria, a decrease in hepatic and ileal reduced glutathione (GSH) and an increase in ileal mucosal lipid peroxidation occur. alpha-Tocopherol (vitamin E) and ascorbic acid (vitamin C) treatment attenuated the incidence of bacterial translocation, improved hepatic and ileal GSH levels and decreased ileal mucosal lipid peroxidation. These results suggest that in chronic PH and CBDL oxidative processes in the liver and intestine play an important role for bacterial translocation.

Topics: Animals; Ascorbic Acid; Bacterial Translocation; Biomarkers; Cholestasis; Common Bile Duct; Glutathione; Hypertension, Portal; Ileum; Intestinal Mucosa; Lipid Peroxidation; Liver; Male; Rats; Rats, Sprague-Dawley; Vitamin E

Experimental venous congestion caused by a 50% constriction of the posterior vena cava results in a shift of some parameters of the carbohydrate metabolism in the rat's pancreas: the content of catecholamines, zinc and ascorbic acid as well as insulin in pancreatic islands. Changes in the content of zinc and ascorbic acid were most demonstrative. Their amount sharply increased within a month from the beginning of experiment.

Topics: Animals; Ascorbic Acid; Catecholamines; Glycogen; Histocytochemistry; Hypertension, Portal; Insulin; Islets of Langerhans; Male; Oxidation-Reduction; Pancreas; Rats; Venae Cavae; Zinc