Nitric Oxide, Platelet Function, Myocardial Infarction and Reperfusion Therapies

Abstract

Abstract. Platelets play an important role in physiologic hemostasis and pathologic thrombosis that complicate the course of vascular disorders. A number of platelet functions including adhesion, aggregation and recruitment are controlled by nitric oxide (NO) generated by platelets and the endothelial cells. Derangements in this generation may contribute to the pathogenesis of thrombotic complications of vascular disorders. The pharmacologic supplementation of the diseased vasculature with drugs releasing NO may help to restore the hemostatic balance.Key Words. nitric oxide, platelet function, myocardial infarction, reperfusion stimulate or inhibit the process of platelet activation. While thromboxane adenosine diphosphate and matrix metalloproteinase-2 mediate the activator platelet reactions [2], prostacyclin, ADPase and NO provide the platelet inhibitor pathways of regulation [3]. These labile mediators control the platelet surface abundance of major platelet receptors including P-selectin, glycoprotein (GP) Ib and GP IIb/IIIa [4][5][6]. The activation of these receptors leads to platelet adhesion to the components of the extracellular matrix and aggregation.Catastrophic events leading to myocardial ischemia and infarction result from atherosclerotic plaque rupture and are mediated to large extent by formation of occlusive platelet thrombus at the site of injury [1]. The objective of this article is to review the actions of nitric oxide (NO) in regulation of platelet function in physiology and during the coronary artery disease. We will also attempt to review the pharmacological effects of NO donors on the diseased coronary circulation.Blood platelets play a vital role in vascular hemostasis. Following an accidental injury, platelets adhere to the damaged portions of the vessel wall and then aggregate forming the hemostatic plug in order to seal the vessel and contain blood loss. This ability of the vasculature must be carefully balanced against the necessity to maintain the fluid state of blood in order to provide oxygen and nutrients to the cells and tissues. A failure to maintain blood in its fluid state leads to thrombosis, one of serious manifestations of vascular dysfunction. In order to maintain tight control over the process of platelet activation, regulatory mechanisms operate as an interactive system of agents that Nitric oxide (NO) is a gaseous biological mediator first identified as the endothelium-derived relaxing factor (EDRF) [7][8][9]. It is generated from the guanidino-nitrogen of L-arginine yielding citrulline (for review see [10]) and plays a prominent role in controlling a variety of functions in the cardiovascular, immune, reproductive, and nervous systems [11][12][13]. The production of NO is catalyzed by three major isoforms of the enzyme NO synthase (NOS): neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) [14][15][16]. The nNOS and eNOS are constitutively expressed and activated by calcium entry into cells [17,18], whereas iNOS is calcium-independent, and its synthesis is induce...

Endogenous Nitric Oxide Protects against T Cell-Dependent Lethality during Graft-versus-Host Disease and Idiopathic Pneumonia Syndrome

“…However, continuous monitoring of blood pressure in allo-BMT mice following AG administration demonstrated a progressive drop in blood pressure in treated mice, indicating that vasoconstrictive effects were not a likely cause of the increased mortality. NO is also known to have potent antithrombotic activity via its ability to inhibit platelet activation, adhesion, and aggregation (49,50). Much of the effect of NO on platelets is derived from NO released by endothelial cells via the eNOS gene.…”

Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

“…[2][3][4][5] This vasorelaxant and platelet regulator is essential for vascular homeostasis and an impairment of NO bioavailability is one of the earliest events in vascular diseases. 6,7 Superoxide anion reacts rapidly with NO producing ONOO -, a major component of oxidative stress, rapidly decreasing NO bioavailability.…”

Enhancement of Endothelial Function Inhibits Left Atrial Thrombi Development in an Animal Model of Spontaneous Left Atrial Thrombosis

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