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- W2066302238 abstract "In a recent PNAS article (1) we demonstrated that endothelial NOS (eNOS) is phosphorylated at Ser-1177, an index of eNOS activation, in HUVEC and blood vessels of rodents challenged with nitroglycerin. In addition, we showed that the time scale in which this phosphorylation happens correlates with the drop in the blood pressure. We have also shown that at <10 nM concentrations nitroglycerin action depends on the endothelium and that above this dose the endothelium removal has little impact on vasodilation in isolated rat aortic rings. Contrary to the allegation by Daiber et al. (2) that our data contradict the literature are demonstrations that nitroglycerin activates eNOS (3, 4). Also, endothelium dependence of nitroglycerin effects, particularly at low concentrations, has been reported in experimental models (5) and in patients (6) with heart failure. The reading of our article reveals that we were aware that eNOS knockout animals are responsive to nitroglycerin. This has been published for some time and was referenced in our study (7). To reconcile our findings with this and other articles showing that impairment of eNOS leads to an improved response to nitroglycerin, we evaluated whether nitroglycerin modulates neuronal NOS (nNOS). Our findings demonstrated that nNOS is sensitive to nitroglycerin, which makes the statement that our article does not make any effort to reconcile our findings with the literature incorrect. We believe that considerable research is still needed to completely understand the mechanisms that lead to vasodilation and endothelial dysfunction, and our article adds to the literature, inviting the investigators of the field to consider eNOS and nNOS as possible mediators of nitroglycerin-induced vasodilation." @default.
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- W2066302238 date "2008-11-19" @default.
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- W2066302238 title "Reply to Daiber et al.: Doubt about an essential role for constitutive nitric oxide synthase in nitroglycerin-mediated vasodilation" @default.
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- W2066302238 doi "https://doi.org/10.1073/pnas.0809563105" @default.
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