Nitric Oxide Delivered By Intraerythrocytic SNOHb To Vascular Smooth Muscle: A Theoretical Analysis

Abstract

Nitric oxide (NO) can be released from multiple enzymatic and non-enzymatic sources to induce vasodilation. We have previously constructed computational models based on the biochemical pathway analysis of constitutive NO synthases in the vasculature and found a large discrepancy between our model predictions and the perivascular NO measurements, suggesting the existence of non-enzymatic or other enzymatic NO sources. S-nitrosohemoglobin (SNOHb) has been hypothesized to carry and release NO-bioactivity to exert an endocrine regulation of vascular tone, but the amount of NO delivered to smooth muscle through this mechanism has not been quantified. In this study, we formulated a multicellular computational model to quantify this NO delivery. Our calculation based on the parameters from published data showed that ~10 pM NO delivered by SNOHb can reach vascular smooth muscle. Whether this amount is capable of solely inducing vasodilation is a subject requiring further investigation. Also, the ~10 pM NO does not account for the paradoxical discrepancy that we have encountered, which suggests that other enzymatic or non-enzymatic sources of NO may exist in the vasculature. We also examined various model parameters and our simulations showed that the NO delivery to smooth muscle by intraerythrocytic SNOHb strongly depends on the concentration and half-life of SNOHb and the erythrocytic membrane permeability to NO.