NO-Oxygen Radical Interactions in Transplant Vasculopathy and Restenosis

NO-Oxygen Radical Interactions in Transplant Vasculopathy and Restenosis  

Balloon injury to the vessel wall removes endothelial sources of NO, derived from the constitutive form of NO synthase. As previously mentioned, recent studies have shown a direct role for NO in the inhibition of vascular lesion development. It is possible, then, that restoration of NO synthase activity in the vessel wall would reestablish vascular function and inhibit neointima formation. 

The stimulation of endogenous -NO synthesis or the addition of exogenous NO donating molecules is thus therapeutic in platelet-mediated ischemic syndromes such as unstable angina and coronary thrombosis. 

There are also other avenues by which -NO may serve a protective role in ischemia-reperfusion phenomena. Under these circumstances, known to include a high rate of production of oxygen free radicals, -NO can react with Oi to divert Oi through ONOO -dependent (and potentially less damaging) oxidative and decomposition pathways. Nitric oxide may also confer protection by reacting with iron to form iron-nitrosyl compounds. By binding free coordination sites of iron, -NO can limit Fenton chemistry and iron-dependent electron transfer reactions (Kanner etal., 1991 Ignarro, 

the decreased availability of -NO during the immediate reperfusion period appears to contribute to the elevated pulmonary resistance and neutrophil recruitment that occurs after lung transplantation. In support of this, augmentation of the -NO pathway enhances lung preservation for transplantation as well as posttransplant survival (Pinsky et al., 1994). 

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