Effects of Arginase I and II on local production of NO

Abstract

Dysfunction of endothelial nitric oxide synthase (eNOS) has been implicated in cardiovascular diseases such as hypertension and diabetes. Arginase I and II (Arg I, II) degrade the substrate for eNOS, L‐arginine and decrease nitric oxide (NO) production. Altered expression and or activity of arginases have been proposed to account for reduced eNOS function in cardiovascular disease and also to provide a mechanism for the “arginine paradox”. Our hypothesis was that ArgI and ArgII inhibit eNOS activity by depleting arginine from specific intracellular pools. To test this hypothesis we transfected COS‐7 cells with arginase I (cytosolic) and arginase II (mitochondria) together with eNOS constructs targeted to various intracellular compartments; namely cytosol, plasma membrane, Golgi, mitochondria and nucleus. In preliminary studies the activity of subcellular eNOS targeting constructs were equally affected by Arg I and II, despite different locations within the subcellular environment. We submit that there are no spatially restricted pools of L‐arginine within COS‐7 cells but a homogenous and equally accessible amount of L‐arginine. Future studies will identify whether endothelial cells possess mechanisms for arginine compartmentalization.