Quantification and regulation of erythrocyte HbNO as an index of vascular NO using EPR spectroscopy
(2019)
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- Abstract
- Reduced nitric oxide (NO) bioavailability is a major feature of endothelial dysfunction characteristic of cardiovascular diseases (CVDs). However, the short half-life of NO precludes an accurate quantification of vascular NO. In red blood cells (RBCs), NO reacts with hemoglobin to form an iron-nitrosyl complex (HbNO), quantifiable by EPR spectroscopy in venous blood ex vivo. We hypothesized that HbNO reflects NO bioavailability and correlates with endothelial function in vivo. We showed that an eNOS in RBC marginally contributes to HbNO, highlighting vascular NO as predominant source for the HbNO complex steady-state level in vivo. We characterized the influence of pO2, T°, pH, reactive oxygen species and RBC antioxidant system on HbNO stability. We identified aquaporin-1 as a peroxiporin that facilitates the H2O2 transport into RBCs. Finally, HbNO correlates with endothelial dysfunction before any clinical manifestation of CVD and inversely with vascular oxidative stress. Our study opens the way to further development of HbNO as a biomarker for early diagnosis and targeted treatment of CVDs with NO-dependent endothelial dysfunction.
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Dei Zotti, F. (2019). Quantification and regulation of erythrocyte HbNO as an index of vascular NO using EPR spectroscopy. https://hdl.handle.net/2078.5/54662