This paper has been peer reviewed.
ARGINASE: A CRITICAL REGULATOR OF NITRIC OXIDE SYNTHESIS AND VASCULAR FUNCTION
Version of Record online: 17 APR 2007
Clinical and Experimental Pharmacology and Physiology
Volume 34, Issue 9, pages 906–911, September 2007
How to Cite
Durante, W., Johnson, F. K. and Johnson, R. A. (2007), ARGINASE: A CRITICAL REGULATOR OF NITRIC OXIDE SYNTHESIS AND VASCULAR FUNCTION. Clinical and Experimental Pharmacology and Physiology, 34: 906–911. doi: 10.1111/j.1440-1681.2007.04638.x
- Issue online: 26 APR 2007
- Version of Record online: 17 APR 2007
- Received 16 February 2006; accepted 1 May 2006.
- endothelial dysfunction;
- nitric oxide synthase;
- smooth muscle cell proliferation
- 1Arginase is the focal enzyme of the urea cycle hydrolysing l-arginine to urea and l-ornithine. Emerging studies have identified arginase in the vasculature and have implicated this enzyme in the regulation of nitric oxide (NO) synthesis and the development of vascular disease.
- 2Arginase inhibits the production of NO via several potential mechanisms, including competition with NO synthase (NOS) for the substrate l-arginine, uncoupling of NOS resulting in the generation of the NO scavenger, superoxide and peroxynitrite, repression of the translation and stability of inducible NOS protein, inhibition of inducible NOS activity via the generation of urea and by sensitization of NOS to its endogenous inhibitor asymmetric dimethyl-l-arginine.
- 3Upregulation of arginase inhibits endothelial NOS-mediated NO synthesis and may contribute to endothelial dysfunction in hypertension, ageing, ischaemia–reperfusion and diabetes.
- 4Arginase also redirects the metabolism of l-arginine to l-ornithine and the formation of polyamines and l-proline, which are essential for smooth muscle cell growth and collagen synthesis. Therefore, the induction of arginase may also promote aberrant vessel wall remodelling and neointima formation.
- 5Arginase represents a promising novel therapeutic target that may reverse endothelial and smooth muscle cell dysfunction and prevent vascular disease.