HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/C1183    most recent 00075.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Zharikov, S. Articles by Patel, J. Search for Related Content PubMed PubMed Citation Articles by Zharikov, S. Articles by Patel, J.

VASCULAR BIOLOGY

Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells

¹Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Florida; ²Malcom Randall Veterans Affairs Medical Center; ³Center for Hypertension, Department of Physiology and Functional Genomics, University of Florida; ⁴Division of Nephrology, Hypertension, and Renal Transplantation, Department of Medicine, University of Florida, Gainesville, Florida

Submitted 11 February 2008 ; accepted in final form 3 September 2008

Elevated levels of serum uric acid (UA) are commonly associated with primary pulmonary hypertension but have generally not been thought to have any causal role. Recent experimental studies, however, have suggested that UA may affect various vasoactive mediators. We therefore tested the hypothesis that UA might alter nitric oxide (NO) levels in pulmonary arterial endothelial cells (PAEC). In isolated porcine pulmonary artery segments (PAS), UA (7.5 mg/dl) inhibits acetylcholine-induced vasodilation. The incubation of PAEC with UA caused a dose-dependent decrease in NO and cGMP production stimulated by bradykinin or Ca²⁺-ionophore A23187. [GenBank] We explored cellular mechanisms by which UA might cause reduced NO production focusing on the effects of UA on the L-arginine-endothelial NO synthase (eNOS) and L-arginine-arginase pathways. Incubation of PAEC with different concentrations of UA (2.5–15 mg/dl) for 24 h did not affect L-[³H]arginine uptake or activity/expression of eNOS. However, PAEC incubated with UA (7.5 mg/dl; 24 h) released more urea in culture media than control PAEC, suggesting that arginase activation might be involved in the UA effect. Kinetic analysis of arginase activity in PAEC lysates and rat liver and kidney homogenates demonstrated that UA activated arginase by increasing its affinity for L-arginine. An inhibitor of arginase (S)-(2-boronoethyl)-L-cysteine prevented UA-induced reduction of A23187 [GenBank] -stimulated cGMP production by PAEC and abolished UA-induced inhibition of acetylcholine-stimulated vasodilation in PAS. We conclude that UA-induced arginase activation is a potential mechanism for reduction of NO production in PAEC.

nitric oxide; endothelial dysfunction; pulmonary hypertension

This article has been cited by other articles:

				S. A. Bainbridge, J. M. Roberts, F. von Versen-Hoynck, J. Koch, L. Edmunds, and C. A. Hubel Uric acid attenuates trophoblast invasion and integration into endothelial cell monolayers Am J Physiol Cell Physiol, August 1, 2009; 297(2): C440 - C450. [Abstract] [Full Text] [PDF]