Treating pulmonary disorders with gaseous agent causing repletion of GSNO

Abstract

Pulmonary disorders in which the GSNO pool or glutathione pool in the lung is depleted and where reactive oxygen species in lung are increased, are treated by delivering into the lung as a gas, agent causing repletion or increase of the GSNO pool or protection against toxicity and does so independently of reaction with oxygen. Agents include ethyl nitrite, NOCl, NOBr, NOF, NOCN, N 2 O 3 , HNO, and H 2 S. Optionally, N-acetylcysteine, ascorbate, H 2 S or HNO is administered in addition to other GSNO repleting agent to potentiate the effect of said agent.

1 . A method for treating a pulmonary disorder associated with depletion of the S-nitrosoglutathione pool in the lung or depletion of the glutathione pool in the lung or production of reactive oxygen species in the lung in a patient having such disorder which comprises delivering into the lungs of said patient as a gas, a therapeutically effective amount of an agent, which causes repletion or increase of the S-nitrosoglutathione pool in the lung or protects against toxicity where glutathione is depleted in the lung or where reactive oxygen species are increased in the lung and does so independently of reaction with oxygen.  
   
   
       2 . The method of  claim 1 , wherein the pulmonary disorder is associated with hypoxemia and/or smooth muscle constriction in the lungs and/or lung infection and/or lung injury.  
   
   
       3 . The method of  claim 1 , wherein the agent is naturally a gas.  
   
   
       4 . The method of  claim 1 , wherein the agent comprises NOX where X is halogen or hydrogen.  
   
   
       5 . The method of  claim 1 , wherein the agent comprises N 2 O 3 .  
   
   
       6 . The method of  claim 1 , wherein the agent comprises H 2 S.  
   
   
       7 . The method of  claim 1 , wherein the agent comprises HNO.  
   
   
       8 . The method of  claim 1 , wherein the agent comprises NOCl.  
   
   
       9 . The method of  claim 1 , wherein the agent comprises NOCN.  
   
   
       10 . The method of  claim 1 , wherein the agent comprises trifluoronitrosomethane.  
   
   
       11 . The method of  claim 1 , wherein the agent comprises methylnitrite.  
   
   
       12 . The method of  claim 1 , wherein the agent comprises ethyl nitrite.  
   
   
       13 . The method of  claim 1 , wherein the agent comprises a compound selected from the group consisting of methylnitrososulfinate, methylthionitrite, thionitrosochloronitrite and thionyldinitrite.  
   
   
       14 . The method of  claim 1 , wherein N-acetylcysteine is also administered, the administration of the N-acetylcysteine being in an amount effective to mediate repletion or increase of the S-nitrosoglutathione pool or potentiate the effect of said agent, in the lung.  
   
   
       15 . The method of  claim 1 , wherein ascorbate is also administered, the administration of the ascorbate being in an amount effective to mediate repletion or increase of the S-nitrosoglutathione pool in the lung and/or protect the lung from injury.  
   
   
       16 . The method of  claim 1 , wherein liquid HNO is also administered, the administration of the HNO being in an amount effective to mediate repletion or increase of S-nitrosoglutathione pool in the lung.