Use of Hydroxyguanidines to Reduce Blood Pressure
- *Abstract
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Nitric oxide has been found to be a critical endogenous regulator of blood flow and thrombosis, a principal neurotransmitter mediating erectile function and a major pathophysiological mediator of inflammation and host defense.Investigators at the Weill Cornell Medical College have been leaders in the study of NO synthases, and in particular have sought to develop compounds and methods to modulate NO production.
Among the suite of patented compounds and methods is one covering methods to enhancing vascular functioning in patients with endothelial dysfunction, tetrahydrobiopterin (BH4) insufficiency or oxidative stres.
More specifically, the investigators found that a predominant reason for NO deficiency in disorders involving endothelial dysfunction is that dihydrobiopterin (BH2) binds to endothelial nitric oxide synthase (eNOS) with affinity equal to the natural cofactor tetrahydrobiopterin (BH4), but that whereas BH4-bound eNOS mediates production of nitric oxide, BH2-bound eNOS does not. Rather BH2-bound eNOS causes diminished nitric oxide to be present by producing superoxide anion that reacts with nitric oxide to inactivate it. BH2-bound eNOS also causes a cascade effect by producing superoxide anion which oxidizes BH4 to BH2 and still greater rate of superoxide production and further diminished production of nitric oxide and increased inactivation of nitric oxide. Oxidative conditions that can predominate in vascular disorders can oxidize BH4 to BH2, thereby initiating this cascade. It is also discovered in the course of making the invention herein that hydroxyarginine, and other hydroxyguanidine-containing molecules can be metabolized to nitric oxide by BH2-bound eNOS.
These patented methods describe the use N- hydroxyguanidine derivatives to produce NO. Patients who will benefit from the treatment include those suffering from coronary artery disease, atherosclerosis, hypertension, diabetes and neurodegeneration.
- *Licensing
- Dan-Oscar Antsonda429@cornell.edu212-746-1297
- 其他
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- 国家/地区
- 美国
