Nitric oxide delivery in stagnant systems via nitric oxide donors: a mathematical model

Abstract

As a small biological molecule, nitric oxide (NO), plays a key role in diverse functions including smooth muscle cell regulation, neurotransmission, inhibition of platelet aggregation, and cytotoxic actions. The assessment of NO effects in biological systems has extensively been studied using NO donor compounds that often have differing NO release mechanisms and kinetic rates. Due to the differing kinetic rates and release mechanisms, in addition to reactions involving NO (such as autoxidation of NO), the NO concentrations to which biological systems are exposed may vary significantly depending upon the NO donor compound. Thus, quantifying the effects of NO using different NO donors is difficult unless the NO concentration profile in the experimental system is predicted or measured. In this study, the spatial and temporal NO concentration in a stagnant system (such as a culture plate or micro-well) is modeled following the addition of an NO donor characterized with first-order NO release kinetics. Two NO donors were utilized: diethylamine NONOate (DEA/NO) and spermine NONOate (SPER/NO). The use of a mathematical model can eliminate the need of complex in situ NO measurements and be useful for predicting the physical loss of NO from the experimental system. In addition, properly scaling the NO concentration can be useful in estimating the maximum NO concentration that will exist in solution. The results show that under widely used in vitro experimental conditions, including varying NO donor concentrations, cellular oxygen consumption rates, and aqueous phase heights, the spatial and temporal NO concentration range can vary significantly. In addition, hypoxic conditions can occur in the vicinity of cells, and in some situations, the physical loss of NO from the experimental system may be significant.