temic vascular resistance by approximately 24% in healthy human subjects. 23 Elevated plasma levels of ADMA are predictive of the increased renovascular resistance observed with aging, hypertension, and heart failure. 24, 25 In patients with renal failure, plasma ADMA levels correlate directly with left ventricular thickness and inversely with ejection fraction, 26 which is consistent with the effect of ADMA to increase systemic resistance.

In normal pregnancy, there is an initial fall in blood pressure and subsequent return toward baseline values in the third trimester. These changes in blood pressure are mirrored by similar changes in plasma ADMA values. In women who develop preeclampsia, plasma ADMA values are elevated. 27 Intriguingly, the impairment of maternal endothelial function and the elevation of plasma ADMA occur before clinical evidence of preeclampsia. 28 These clinical studies are supported by experimental studies with cell culture or isolated vessels demonstrating that ADMA inhibits endothelium-dependent vasodilation and/or NO synthesis. 1, 29 In mice genetically engineered to express low plasma ADMA levels, NO synthesis is increased, and vascular resistance is reduced. 30