Reactive oxygen species (ROS) are important modulators of vascular reactivity. Coronary artery disease (CAD) changes the mechanism of human arteriolar flow-mediated dilation (FMD) from NO to hydrogen peroxide (H2O2), a signaling ROS. Evidence suggests that mitochondrial ROS (mtROS) production and the longevity of a cell or organism are inversely related. Nuclear telomerase activity (TA), prevents cellular senescence and tissue aging, and shows a reciprocal relationship with mtROS production. Recently telomerase activity has been identified in the mitochondria where its ability to regulate. mtROS production could increase NO bioavailability, restoring vascular function. Pro-atherosclerotic factors have been shown to inactivate telomerase [1]. Two antagonistic components of the renin angiotensin system, ANG II (pro) and ANG 1-7 (anti), have long been implicated in atherosclerosis. ANG II down-regulates telomerase activity in the endothelium, through accumulation of ROS [2]. This could explain the elevation in blood pressure seen in telomerase-deficient mice. ANG 1-7, a counter regulator to the actions of ANG II, increases NO bioavailability [3], decreases production of ROS [4], is anti-atherosclerotic and causes vasodilation [5]. Therefore, we hypothesize that ANG 1-7 operates through a mechanism involving stimulation of telomerase activity to reduce mitoROS production and restore the NO-mediated mechanism of dilation to shear in patients with CAD. Human coronary arterioles (~200 µm) from discarded atrial and visceral adipose tissue were cannulated for videomicroscopy. Dilation to graded degrees of shear was measured in vessels constricted with endothelin-1. Pharmacological inhibition of TA (BIBR 1532; 10 μM 15-20 h) in vessels from healthy individuals shifted the mechanism of FMD from NO to H2O2 (Figure 1). In arterioles from patients with CAD, ANG 1-7 (1 nM 15-20 h) shifted the mechanism of FMD from H2O2 to NO. This effect was prevented by BIBR 1532 (Figure 2). To evaluate if ANG 1-7 enhances telomerase expression by increasing expression, we used cultured endothelial cells (HUVECs) treated with either vehicle or ANG 1-7 (1 nM). Western blot analysis (Figure 2, right) suggests an increase in telomerase expression after ANG 1-7 treatment. We conclude that ANG 1-7 increases telomerase activity in the vasculature, which plays a critical and acute role in modulating microvascular function.