Pharmacology of nitric oxide NO

Nitric oxide is a mediator that is very different from any other hormones and transmitters. Three key properties of NO are important to its unique mode of signal transmission  

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The source of nitric oxide was diethylenetriamine/nitric oxide, DETA/ NO (Scheme 20.4) a compound that has been used in studies of the cytostatic, vasodilatory and other pharmacological properties of NO [65-67]. DETA/NO is a 1-substituted diazen-l-ium-l,2-diolate containing the [N(0)N0] functional group that has been proved to be useful for the reliable generation of nitric oxide in homogenous solutions [68]. When dissolved in blood, cell culture medium or buffer this compound dissociates to generate NO leaving the nucleophilic structure as a by-product. 

Gulati, K., Chakraborti, A., Ray, A. (2007). Stress-induced modulation of the neuro-immune axis and its regulation by nitric oxide (NO) in rats. In Proceedings of 40th Annual Conference of the Indian Pharmacological Society, NIPER, Mohali, p. 76. 

The dichloromethane extract from Wilbrandia ebracteata (p.o.) significantly reduced the paw elevation time (1 mg/kg) and cell influx (10 mg/kg) in zymosan-induced arthritis in rats. The same extract inhibited COX-2 activity, as measured by PGE2 production, without affecting that of COX-1. Moreover, nitrite release was clearly and significantly reduced at a dose of 10 mg/kg (p.o.). The analysis of the pharmacological data, together with the HPLC analysis of the extracts, points to an anti-inflammatory effect based on an associated reduction in nitric oxide (NO) release and COX-2 inhibition by the cucurbitacins... 

When the effect of nitric oxide donors on cGMP-accumulation is studied, one must take into account the rate of NO-release from the donor compound The diffusion rate of NO is quite high, because of the small size and hpophihcity of this molecule (45), Sodium nitroprusside (SNP) is often used an NO-donor. This compound is inexpensive, which is an important asset. However, the byproduct after NO-release, [Fe(CN)5], is not devoid of pharmacological activity (46) In addition, SNP is light sensitive, although in most cases this property should not rule out use of this compound. In 10-min incubations with brain slices, SNP and the NO-donors S-nitroso-acetyl-penicillamine and streptozotocin were equally effective in raising cGMP levels (unpublished). 

In view of the fact that pharmacological effects of nitroprusside, [Fe(CN)5NO], a widely recognized hypotensive agent (61—65), have been attributed to the release of nitric oxide from its reduced form, i.e., [Fe(CN)5NO], the kinetic and thermodynamic properties of both nitrosyl complexes of pentacyanoferrate-(II) and -(III) have attracted considerable attention in the past two decades (66,67). In this context, the formation of [Fe(CN)5NO] and [Fe(CN)5NO] in the direct reactions of [Fe(CN)5(H20)] and [Fe(CN)5(Fl20)] with nitric oxide, respectively, was subjected to detailed kinetic and mechanistic investigations (68-70). As presented below, the results of these studies allowed to draw valuable conclusions concerning the validity of the mechanism of NO release from nitroprusside postulated in the Hterature. 

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