NO Break-Ins at Water Gate

Abstract

Nitric oxide (NO) is a gaseous free radical that functions as an endogenous mediator in diverse biological effects in numerous tissues. In the kidney and vasculature, these processes include the control of systemic and microvascular tone, the glomerular microcirculation, renal sodium excretion, and inflammatory responses in the glomerulus and tubulointerstitium, among many others.1 NO also impacts the renin–angiotensin and eicosanoid systems, endothelin, cytokines, and other key regulators of inflammation. Because of its potent chemical reactivity, high diffusibility, and the fact that, unlike most endogenous chemical signals, it cannot be stored or secreted, NO production by NO synthases is under complex, tight control to dictate specificity of its signaling and to limit toxicity to other cellular components. These controls serve to govern the timing, magnitude, and spatial distribution of NO release, and, in turn, specify the input signals that activate NO release and the effector functions of the molecule to target specific proteins. The biological role of NO as an inter- and intracellular messenger molecule is greatly dependent on its effective concentration and bioavailability at sites of action. As a hydrophobic gas, NO has traditionally been thought to traverse freely across cell membranes without the need for a specific transport protein to facilitate diffusion. It is also known that NO may accumulate in cellular lipids and preferentially interact with molecules in lipid environments. Since cellular entry of NO has generally been regarded to be near diffusion-limited, many of the reactions of NO are thought to depend on the rate of collision between NO and its target molecules or functional groups. Proteins that are structurally or …