Nitric oxide signalling and its role in the activation of human blood platelets

Sheikh Arshad Saeed, Muhammad Anwar Waqar, Muhammad Atif Waqar, Syed Faraz Kazim, Aabdul Basit, Nabeel Ahmad

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Nitric oxide (NO) is increasingly being recognised to play a pivotal role in numerous physiological and pathophysiological processes throughout the human body. Many cardiovascular diseases are associated with a reduction in the activity of endothelium-derived NO as an important component involved in the initiation and/or progression of the disease. We have previously reported that NO donor S-Nitroso-N-acetylpenicillamine (SNAP) strongly inhibits signal transduction mediated by various platelet agonists. NO activates guanylate cyclase as a common effector mechanism that results in reduced free cytoplasmic calcium, inhibition of platelet phosphatidylinositol 3-kinase (P 1-3), and reduction in the affinity and number of surface membrane fibrinogen-binding sites, (GpIIb/ IIIa). NO also acts in synergy with prostacyclin (PGI 2), an eicosanoid released from the endothelium, and potentiates anti-aggregatory effects. Prostacyclin inhibits platelet aggregation by increasing the intracellular concentration of cyclic adenosine monophosphate (cAMP). The possibility of using NO donors to inhibit platelet activation in vivo, such as in arterial thrombosis is currently being explored. Drugs such as nitroglycerin (GTN) are known to act as NO donors, but the vasodilator effects are much greater than tfieir antiplatelet activity. One drug that boosts the physiological effects of NO is Sildenafil which blocks the breakdown of cyclic guanosine monophosphate (cGMP) and thereby amplifies the biological effects of NO in the corpus cavernosum - this is how it works to improve the erectile function. NO being one of the simplest mediators has some of the most complex actions and provides myriad opportunities for new treatments.

Original languageEnglish
Pages (from-to)357-363
Number of pages7
JournalJournal of the Chemical Society of Pakistan
Issue number4
Publication statusPublished - Aug 2007
Externally publishedYes


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