| Summary: | Historically nitric oxide (NO) was viewed as playing a purely paracrine role in the vasculature, acting within the vicinity of its release. Today an endocrine role of NO metabolites is widely accepted, although the species accounting for the vascular regulatory function still remains in contention. The original aim of this thesis was to analyse the two main NO metabolite hypotheses (i.e., SNO-Hb and nitrite hypotheses) to provide a more comprehensive understanding of their potential significance in the human circulation. Initially this involved developing methods capable of measuring baseline levels of NO metabolites in human blood. During this work a major confounding factor was identified influencing the measurement of NO attached to red blood cells/haemoglobin. A means was developed to overcome this via the modification an assay reagent, which was used along with several other methods to analyse NO metabolites in human blood. Ultimately however, levels of SNO-Hb at baseline were on the border of methodological sensitivity, although haemoglobin-bound NO was distinguishable. Consequently my work focused on the potential of nitrite versus haemoglobin-bound NO per se to act as endocrine NO metabolites in the human vasculature. Nitrite metabolism in human whole blood was analysed whilst the vasodilatory properties of nitrite were investigated in relation to the relaxation response observed from native red blood cells under hypoxic conditions. Finally for the first time ever NO metabolites were measured across the coronary and pulmonary vascular beds in the human circulation to address their potential to regulate vascular tone at baseline and under conditions of increased oxygen demand.
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