Molecular Mechanisms of Action of Gas Transmitters NO, CO and H2S in Smooth Muscle Cells and Effect of NO-generating Compounds (Nitrates and Nitrites) on Average Life Expectancy.

Gaseous signaling molecules (gas transmitters) take an especial position among the numerous signaling molecules involved in the regulation of both intracellular processes that occur in different types of cells and cell-cell interactions. At present time, gas transmitters include three molecules whose enzymatic systems of synthesis and degradation, physiological action and intracellular effectors, the change of which under the action of gas transmitters may result in physiological and/or pathophysiological effects are well- determined. These molecules include nitrogen oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). They are involved in the regulation of functions of various organs and systems of the human body, including the circulatory system. Interaction of NO, CO and H2S with various enzymatic and structural components of endothelial and, especially, smooth muscle cells has a significant impact on vascular tone and blood pressure. Furthermore, the crossing of NO-, CO- and H2S-mediated signaling pathways at common effectors and interaction with each other can determine the end, resulting functional response of the cell. The knowledge of the molecular targets of gas transmitters' action, the structure of the binding centers for gas transmitters and their interaction with each other may be essential in the development of methods of regulation of these signaling systems by targeted, directed action. This review summarizes the molecular mechanisms of the NO, CO and H2S interaction with the main targets, which carry out their regulatory effect on vascular smooth muscle cells. Also we describe here different ways of cross-regulation of NO-, CO- and H2S-dependent signaling pathways. We analyzed NO-synthase and nitrite reductase systems of nitric oxide cycle and discuss the nitrate-nitrite background of the existence of modern man, which can substantially modify the signaling system, the metabolism of virtually all cell ultrastructure of neurons, neuron-neuron and neuron-glial interactions and exerts its influence on socially significant diseases that can affect the quality and the average life expectancy.