Method and formulation for treating vascular disease

Abstract

A therapeutic mixture comprised of L-arginine and inhibitors of Hmg-CoA-Reductase is disclosed for the treatment of diseases related to endothelial dysfunction, wherein the endothelial dysfunction is relieved by stimulating the constitutive form of nitric oxide synthase (cNOS) to produce native nitric oxide (NO).

Description

BACKGROUND OF THE INVENTION [0001] This invention relates generally to a method of treating cardiocerebrorenovascular disease as well as avoiding potential cardiocerebrorenovascular disease, and the symptoms thereof, wherein a substrate of Nitric Oxide Synthase (“NOS”) and an agonist of NOS are combined to produce a beneficial effect. DESCRIPTION OF RELATED ART [0002] Much focus in the area of cardiac disease has been on the presence of cholesterol in the body. Hypercholesterolemia is known to be a primary risk factor for death from coronary heart disease. It is known that 50% or more of the total body cholesterol in humans is derived from intrinsic biosynthesis. It is also known that a rate-limiting step of major significance in the biosynthesis of cholesterol is at the level of the enzyme known as 3-hydroxy-3-methylglutaryl-coenzyme A reductase or Hmg-CoA reductase. A general class of compounds is known in the art which inhibit and reduce the intrinsic biosynthesis of cholesterol ...

AI Technical Summary

Benefits of technology

[0016] It is an object of this invention to provide a method of preventing, treating, arresting, or ameliorating disease conditions which are benefited by the bio-transformation of a substrate into endogenous nitric oxide or “native” nitric oxide.

[0017] It is another object of this invention to provide a method of preventing, treating, arresting, or ameliorating disease conditions which are benefited by the bio-transformation of L-arginine into “native” nitric oxide through enzyme activation of NOS.

[0018] It is another object of this invention to ameliorate or avoid tachycardia and prevent or treat ischemia.

[0019] It is another object of this invention to achieve a beneficial effect when treating disease conditions by increasing or maximizing the production of “native” nitric oxide, and reducing clinical endpoints to include mortality.

[0020] It is another object of this invention to prevent reperfusion injury in subjects who have had abrupt restoration of blood flow.

[0027] Yet another embodiment is a method for stimulating cNOS in a subject which comprises: selecting a subject; administering to said subject a formulation comprising a mixture of L-arginine and inhibitors of Hmg-CoA reductase, so as to maximize “native” NO production and reduce endpoints to include mortality.

Problems solved by technology

Hypercholesterolemia is known to be a primary risk factor for death from coronary heart disease.

The induced form of the enzyme produces much greater amounts of NO than the constitutive form, and induced NOS appears to be the “pathophysiological” form of the enzyme because high concentrations of NO produced by iNOS can be toxic to cells.

However, until now there was no known research indicating Hmg-CoA reductase inhibitors were capable of functioning as agonist of cNOS.

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