| Objective: The synthesis of nitric oxide (NO) from the ammo acid L-arginine is catalyzed by the enzyme nitric oxide synthase (NOS). NO mediates vasodilation and inhibits platelet aggregation, thrombus formation, expression of adhesion molecules and chemokines for leukocytes, and oxidative stress. It also attenuates growth and proliferation of vascular smooth muscle cells. Up to date, three distinct NOS isoforms have been described based on cloning of their cDNAs, genomic sequences, and chromosomal localization; neuronal NOS (nNOS), cytokine-inducible NOS (iNOS), and endothelial NOS (eNOS). The eNOS and nNOS belong to the constitutive type of NOS (eNOS), while iNOS, under normal conditions, is not expressed in blood vessels. Exposure to lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-a), and some other proinflammatory cytokines, however, can stimulate expression of iNOS in blood vessels. iNOS is expressed only following transcriptional activation of its gene as in acute and chronic inflammation. Biosynthesis of NO protein and iNOS mRNA has been increasingly recognized as an important intra- and intercellular messenger molecule in vascular relaxation, platelet activation and immune response in human mononuclear cells. It plays important roles in the pathogenesis of Gram-negative septic shock and other infectious diseases. Endothelium-derived NO, synthesized by the constitutively expressed eNOS, plays a significant role in the maintenance of basal vascular tone and regulation of blood pressure.Coronary heart disease (CHD), that is, ischemic heart disease (IHD), is considered to be one of the leading causes of death among people all over the world. It includes coronary atherosclerotic heart disease and coronary spasm. While extensive and deep research on mechanisms contributing to the pathogenesis of IHD has been underway. It is well known that hypertension is one of the high-risk factors in the pathogenesis of IHD. Several previous studies elucidated in Japan have suggested that eNOS gene polymorphisms was associated with hypertension or coronary spasm in Japanese. They found T-786→C mutation in the eNOS gene reduces the endothelial NO synthesis and predisposes the patients with the mutation to IHD. Their foundingstrongly suggest that eNOS, as a genetic risk factor, has a genetic association with the pathogenesis of IHD. It not only provides a novel theory to the pathogenesis of IHD, but also develops a new clinically relevant therapeutic target for IHD.Dingxi recipe (DXR) is formed with the theory of traditional Chinese medicine (TCM). It shows great therapeutic effects in preventing and treating IHD in clinical application. Cardiac arrhythmias are the major clinical manifestations of IHD. Our previous studies show: DXR can improve the blood NO concentration to treat the cardiac arrhythmias induced by myocardial ischemia and(or) myocardial ischemic and reperfusion injury. However, the precise mechamism(s) remains unclear. [Panax notoginseng (Burk.) F.H. Chen] is one of the major compositions of DXR. Current pharmacological study demonstrates that total Panax Notoginseng Saponins (tPNS), the major active substance of [Panax notoginseng (Burk.) F.H. Chen] , is consisted of three momoners: Rbl, Rgl and Rl. Clinical and experimental evidences indicated that tPNS mediates vasodilation of coronary, and inhibits platelet aggregation and thrombus formation. It also attenuates growth and proliferation of vascular smooth muscle cells. In general, tPNS shows great therapeutic effects in preventing and treating in atherosclerosis (AS) and IHD. Now it is widely used in clinical treatment with many types of preparations. Both interior and exterior NO mediate vasodilation of all kinds of vessels, including artery, vein, coronary et al. tPNS can enhance the release of NO from the cultured porcine aorta endothelial cells. In summary, the vasodilative effect of tPNS is due to the release of NO. Recently, a lot of hypothesis about tPNS promoting the synthesis of NO on cell level has been revealed.Since the hu...
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