Abstract 16718: Energy Induced Vasodilation in a Model of Endothelial Dysfunction Requires Nitric Oxide
Introduction: Over 8 million Americans are treated for peripheral artery disease (PAD), i.e. intermittent claudication, impaired wound healing, and critical limb ischemia. Endothelial dysfunction of the microcirculation is a potential mechanism for the pathogenesis of PAD because risk factors for PAD- age, hypertension, atherosclerosis, diabetes mellitus, and active tobacco use, have been directly related to a reduction in NOS expression and NO production. These reductions in NO bioavailability impair flow mediated dilation of the brachial artery and acetylcholine induced vasodilation. We have shown energy (670 nm (R/NIR)) can increase NO independent of NOS through release of NO from nitrosyl-heme stores. We hypothesized R/NIR can stimulate vasodilation, and serve as a potential therapy to recover vasodilation in a model of endothelial dysfunction (db/db mice).
Methods: Human dermal microvascular endothelial cells (HMVEC) loaded with DAF-2 were stimulated with R/NIR 100mW/cm2 up to 6J. NO was measured using HPLC of DAF-2T. To test vasodilation, facial arteries from C57Bl/6 and db/db mice were isolated, pressurized to 60mmHg, and pre-constricted with U46619. The vessels were irradiated with 670 nm light (10mW/cm2) for 5 min with 10 min dark period between irradiation.
Results: HMVEC stimulated with R/NIR increased NO 28.3% (±11.2, p<0.05). The NO scavenger c-PTIO inhibited R/NIR (17.0%±5.9, p<0.05) but was unchanged by pre-incubation with NOS inhibitor L-NAME (1mM) (13.1% ± 5.6). Vessel diameter increased up to 17.8% (±3, p<0.05) after 5 min with R/NIR. L-NAME did not affect dilation (13.74% ±2.2), however c-PTIO (100μM) could attenuate dilation (-.51% ± 1.1, p<0.001). R/NIR vasodilation was abolished with vessel denudation (1.2%± 2.21, p<0.001), suggesting R/NIR dilation was endothelial dependent. Impaired dilation in db/db mice was reversed, as R/NIR could significantly dilate db/db vessels after 5 min [(13.7% ± 2.8) vs. control (17.8% ±3)].
Conclusion: R/NIR vasodilation requires intact endothelium and NO, but does not require NOS. In an obesity model of endothelial dysfunction, R/NIR can significantly restore vasodilation. Therefore, R/NIR as a source for therapeutic NO should be strongly considered in the treatment of ischemic wounds.
Author Disclosures: B. Lindemer: None. D. Weihrauch: None. A. Keszler: None. N. Lohr: None.
- © 2015 by American Heart Association, Inc.