Use of S-Nitrosothiol Signaling to Treat Disordered Control of Breathing

Abstract

The present invention is directed to a method of treating disordered control of breathing including the treatment of apnea and hypoventilation associated with congenital or acquired brain stem abnormalities. Specifically the invention is directed to treating disordered control of breathing by administering an S-nitrosylating agent selected from the group consisting of ethylnitrite, glutathione, nitric oxide, S-nitrosocysteine, S-nitrosoglutathione, S-nitroso-L-cysteinyl glycine, N-acetyl cysteine and S-nitroso-N-acetyl cysteine. As shown in FIG. 1 C the ability of endogenous SNOs to increase V E in freely behaving, conscious rats using whole-body plethysmography revealed that CSNO, GSNO and CGSNO (1 nmol each) caused equivalent increases in V E , whereas D-CSNO had no effect (left bar graph is the control whereas the right bar represents administration of the respective SNO).

1 - 62 . (canceled) 
     
     
         63 . A method of treating disordered control of breathing or disordered breathing, said method comprising the step of administering to an individual a composition comprising an S nitrosylating agent, wherein the S nitrosylating agent is selected from the group consisting of ethyl nitrite, glutathione, S-nitroso L cysteinyl glycine, N-acetyl cysteine, S-nitroso N acetyl cysteine, and nitric oxide, wherein when said composition comprises nitric oxide said composition said composition is administered by inhalation. 
     
     
         64 . The method of  claim 63 , wherein the S nitrosylating agent is administered via a route selected from the group consisting of parenterally, intravenously, subcutaneously, intramuscularly, transdermally, inhalation, and orally. 
     
     
         65 . The method of  claim 63 , wherein said disordered control of breathing is at least one condition selected from the group consisting of: apnea, central apnea, obstructive sleep apnea, hypoventilation, central hypoventilation, congenital central hypoventilation syndrome, impaired control of peripheral respiratory drive, impending respiratory failure, respiratory fatigue complicating obstructive lung disease, impaired respiratory drive, impaired respiratory drive associated with chronic obstructive pulmonary disease, impaired respiratory drive associated with emphysema, impaired respiratory drive associated with chronic bronchitis, impaired respiratory drive associated with cystic fibrosis, and impaired respiratory drive associated with α-1 antitrypsin deficiency. 
     
     
         66 . The method of  claim 63 , wherein the S nitrosylating agent is formulated with at least one pharmaceutically acceptable carrier. 
     
     
         67 . The method of  claim 63 , wherein the S nitrosylating agent is formulated with at least one pharmaceutically acceptable diluent. 
     
     
         68 . The method of  claim 63 , wherein the S nitrosylating agent is formulated with at least one pharmaceutically acceptable solubilizing agent. 
     
     
         69 . A kit for treating disordered control of breathing, said kit comprising an S-nitrosylating agent selected from the group consisting of ethyl nitrite, glutathione, S-nitroso L cysteinyl glycine, N-acetyl cysteine, S-nitroso N acetyl cysteine, and nitric oxide; and reagents for detecting and monitoring the in vivo concentration of S-nitrosothiols; and instructional materials for use. 
     
     
         70 . A kit for increasing minute ventilation (VE) at the level of the brainstem respiratory control centers in the nucleus tractus solitarius of an individual, said kit comprising an S-nitrosylating agent selected from the group consisting of ethyl nitrite, glutathione, S-nitroso L cysteinyl glycine, N-acetyl cysteine, S-nitroso N acetyl cysteine, and nitric oxide; and reagents for detecting and monitoring the in vivo concentration of S-nitrosothiols; and instructional materials for use.