Pharmacology of NO Generation and Action in the Platelet Microenvironment

4 Nitric oxide donors and their clinical relevance as inhibitors of platelet activation 

Mechanism of pharmacological activity of NO donors is most probably related to the release of NO (Feelisch and Noack 1987). As these compound release NO in a ntaneous, catalyst- or enzyme-dependent marmer the biological effects of compounds ate usually longer lasting when compared with NO gas. 

Whether or not platelets similar to the vessel wall become tolerant to the platelet-inhibitory effects of organic nitrates is again controversial (Weber et al 1996 Booth et al 1996). There have been many attempts to synthesise tolerance-free NO donors. One of more promising groups of drugs are cysteine-containing nitrates. The incorporation of a cellular 

The phenomenon of tolerance is of lesser pharmacological significance for other NO donors including sodium nitroprusside, molsidomine and SIN-1. 

Because of its powerfiil vasodilator action sodium nitroprusside is often used to treat vascular emergencies associated with hypertensive crisis. Since this compound shows some anti-platelet activity both in vitro and in vivo (Levin et al 1982, Hines and Barash 1989) its acute clinical effects may also be mediated, in part, through inhibition of platelet function. Recently, sodium nitroprusside was administered intrapericardially to treat experimentally induced coronary Arombosis in dogs (Willerson et al 1996). As this route of administration of sodium nitroprusside produced less vasodilatation than systemic one, localized administration of this dmg may offer new therapeutic possibilities for the treatment of the coronary thrombosis. 

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