Enhancement of vascular function by modulation of endogenous nitric oxide production or activity

Abstract

Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. Alternatively, or in combination, other compounds may be administered which provide for short term enhancement of nitric oxide, either directly or by physiological processes

What is claimed is:  
     
         1 . A method of improving function and structure of the vascular system of a human host, said method comprising: 
 administering orally to said host in accordance with a predetermined regimen a prophylactic dose of a source of at least one of L-arginine and L-lysine as other than a natural food source to enhance the level of endogenous NO in the vascular system to improve vascular function.    
     
     
         2 . A method according to  claim 1 , wherein said dose comprises at least 50% by weight of at least one of amino acid compounds L-arginine or L-lysine, polypeptides comprising at least about 40 mol % of at least one of said amino acids, or physiologically acceptable salt thereof.  
     
     
         3 . A method according to  claim 2 , wherein said polypeptide is an oligopeptide of at least one of L-arginine and L-lysine.  
     
     
         4 . A method according to  claim 2 , wherein said dose comprises L-arginine.  
     
     
         5 . A method according to  claim 4 , wherein L-arginine is administered in a daily amount in the range of 1 to 25 g per day.  
     
     
         6 . A method according to  claim 4 , wherein L-arginine is administered at a dosage in the range of 0.5 to 5 g per dose.  
     
     
         7 . A method according to  claim 2 , wherein said dose comprises L-lysine.  
     
     
         8 . A method according to  claim 7 , wherein L-lysine is administered in a daily amount in the range of 1 to 25 g per day.  
     
     
         9 . A method according to  claim 7 , wherein L-lysine is administered at a dosage in the range of 0.5 to 5 g per dose.  
     
     
         10 . A method according to  claim 1 , wherein said dose comprises at least one of calcium, an amino acid absorption enhancing compound, a cofactor for NO synthase activity, or an antioxidant in an amount sufficient to enhance the prophylactic effect of said L-arginine and L-lysine.  
     
     
         11 . A method according to any of claims  5 ,  6 ,  8  or  9 , wherein said dose is administered as a tablet, capsule, or powder.  
     
     
         12 . A method according to claims  5 ,  6 ,  8  or  9 , wherein said dosage is administered as a prepared solid food, nutritional supplement or liquid.  
     
     
         13 . A method of preventing a reduction in vascular function of the vascular system of a human host as evidenced by reduced vasodilation, said method comprising: 
 administering orally to said human host in accordance with a predetermined regimen a prophylactic dosage of at least one of L-arginine, L-lysine or physiologically acceptable salt thereof as other than a natural food source in a daily amount to provide a plasma level in the range of 0.15 to 3 mM to enhance the level of endogenous NO in the vascular system,    whereby reduction in said vasodilation is inhibited.    
     
     
         14 . A method according to  claim 14 , wherein said L-arginine, L-lysine or a physiologically acceptable salt thereof is present in a prepared food, nutritional supplement or liquid at from about 0.5-25 g.  
     
     
         15 . A method according to  claim 13 , wherein said dose of L-arginine, L-lysine or a physiologically acceptable salt thereof, is in the range of 0.5-10 g in combination with at least one of calcium, folate, B 12  or B 6  in sufficient amount to enhance the effect of said L-arginine, L-lysine or a physiologically acceptable salt thereof.  
     
     
         16 . A method according to  claim 13 , wherein said L-arginine, L-lysine or its physiologically acceptable salt is administered as a tablet, capsule, or powder.  
     
     
         17 . A physiologically acceptable formulation comprising at least one of L-arginine, L-lysine or its physiologically acceptable salt in from about 0.5 to 5 g and at least one of calcium, folate, B 6 , or B 12 , in sufficient amount to enhance the effect of said L-arginine, L-lysine or its physiologically acceptable salt on enhancing the amount of NO in a human host.  
     
     
         18 . A physiologically acceptable formulation comprising L-arginine or its physiologically acceptable salt.  
     
     
         19 . A physiologically acceptable formulation comprising L-lysine or its physiologically acceptable salt.  
     
     
         20 . A method for inhibiting vascular smooth muscle cell proliferation at a site of injury in the vascular system, said method comprising: 
 administering at said site an effective amount of at least one of L-arginine, L-lysine or its physiologically acceptable salt to enhance NO production;    whereby vascular smooth muscle cell proliferation is inhibited.    
     
     
         21 . A method according to  claim 20 , wherein said injury is as a result of angioplasty.