Angiotensin 1-7 treatment restored the nitric oxide component of flow-mediated dilation in arterioles from patients with coronary artery disease in a telomerase-dependent manner.
Does angiotensin 1-7 restore the nitric oxide component of flow-mediated dilation in human arterioles from patients with CAD?
Angiotensin 1-7 exerts vasoprotective effects in the human microvasculature by restoring NO-mediated dilation via modulation of telomerase activity.
OBJECTIVE: This study examined vascular actions of angiotensin 1-7 (ANG 1-7) in human atrial and adipose arterioles. APPROACH AND RESULTS: The endothelium-derived hyperpolarizing factor of flow-mediated dilation (FMD) switches from antiproliferative nitric oxide (NO) to proatherosclerotic hydrogen peroxide in arterioles from humans with coronary artery disease (CAD). Given the known vasoprotective properties of ANG 1-7, we tested the hypothesis that overnight ANG 1-7 treatment restores the NO component of FMD in arterioles from patients with CAD. Endothelial telomerase activity is essential for preserving the NO component of vasodilation in the human microcirculation; thus, we also tested whether telomerase activity was necessary for ANG 1-7-mediated vasoprotection by treating separate arterioles with ANG 1-7±the telomerase inhibitor 2-[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-ylamino]benzoic acid. ANG 1-7 dilated arterioles from patients without CAD, whereas dilation was significantly reduced in arterioles from patients with CAD. In atrial arterioles from patients with CAD incubated with ANG 1-7 overnight, the NO synthase inhibitor NG-nitro-l-arginine methyl ester abolished FMD, whereas the hydrogen peroxide scavenger polyethylene glycol catalase had no effect. Conversely, in vessels incubated with ANG 1-7+2-[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-ylamino]benzoic acid, NG-nitro-l-arginine methyl ester had no effect on FMD, but polyethylene glycol catalase abolished dilation. In cultured human coronary artery endothelial cells, ANG 1-7 significantly increased telomerase activity. These results indicate that ANG 1-7 dilates human microvessels, and dilation is abrogated in the presence of CAD. Furthermore, ANG 1-7 treatment is sufficient to restore the NO component of FMD in arterioles from patients with CAD in a telomerase-dependent manner. CONCLUSIONS: ANG 1-7 exerts vasoprotection in the human microvasculature via modulation of telomerase activity.
Durand et al. (Fri,) conducted a other in Coronary artery disease. Angiotensin 1-7 vs. Telomerase inhibitor or non-CAD arterioles was evaluated on Flow-mediated dilation (FMD). Angiotensin 1-7 treatment restored the nitric oxide component of flow-mediated dilation in arterioles from patients with coronary artery disease in a telomerase-dependent manner.