Vascular arginase and hypertension

Hypertension has been associated with both decreased production of the potent vasodilator nitric oxide (NO) and vascular remodeling. L-arginine is the substrate for endogenous NO production by the NO synthases (NOS). L-arginine is also the substrate for the arginases, which metabolize L-arginine to L-omithine and urea. There are 2 described isoforms of arginase, arginase I and arginase II; both isoforms are inducible and widely expressed in the body. Recently, it has been found that arginase I and II are expressed in vascular tissue, and that arginase activity can be induced by many hypertensive stimuli, including chronic inflammation and salt loading. Induction of arginase activity results in decreased L-arginine bioavailability to NOS and thereby may decrease the endogenous production of NO in the vasculature. Furthermore, L-omithine produced by arginase can be further metabolized to polyamines and proline, which are central to vascular smooth muscle cell proliferation and vascular remodeling. Thus, arginase is involved in the pathogenesis of hypertension by promoting vascular remodeling and attenuating the endogenous production of NO. This review will examine the regulation of arginase expression and its role in the pathogenesis of hypertension, as well as the therapeutic potential of arginase inhibition for treating some forms of hypertension.