Use of nitrite salts for the treatment of cardiovascular conditions

Abstract

It has been surprisingly discovered that administration of nitrite to subjects causes a reduction in blood pressure and an increase in blood flow to tissues. The effect is particularly beneficial, for example, to tissues in regions of low oxygen tension. This discovery provides useful treatments to regulate a subject's blood pressure and blood flow, for example, by the administration of nitrite salts. Provided herein are methods of administering a pharmaceutically-acceptable nitrite salt to a subject, for treating, preventing or ameliorating a condition selected from: (a) ischemia-reperfusion injury (e.g., hepatic or cardiac or brain ischemia-reperfusion injury); (b) pulmonary hypertension (e.g., neonatal pulmonary hypertension); or (c) cerebral artery vasospasm.

1 . A method of treating pulmonary hypertension in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a non-acidified pharmaceutically acceptable nitrite salt. 
     
     
         2 . The method of  claim 1 , wherein the non-acidified pharmaceutically acceptable nitrite salt is an alkali metal nitrite. 
     
     
         3 . The method of  claim 1 , wherein the non-acidified pharmaceutically acceptable nitrite salt is a salt of an anionic nitrite with a cation, which is selected from sodium, potassium, and arginine. 
     
     
         4 . The method of  claim 1 , wherein the non-acidified pharmaceutically acceptable nitrite salt is non-acidified sodium nitrite. 
     
     
         5 . The method of  claim 1 , wherein the administration is by an administration route, in which the non-acidified pharmaceutically acceptable nitrite salt contacts blood of the subject. 
     
     
         6 . The method of  claim 5 , wherein the administration route is selected from the group consisting of intravenous, intramuscular, rectal, ex vivo, intraocular, intraperitoneal, intraarterial, subcutaneous, and into a cardiopulmonary bypass circuit. 
     
     
         7 . The method of  claim 1 , wherein the subject has primary pulmonary hypertension. 
     
     
         8 . The method of  claim 1 , wherein the subject has secondary pulmonary hypertension. 
     
     
         9 . The method of  claim 1 , wherein the subject has primary and secondary pulmonary hypertension. 
     
     
         10 . The method of  claim 1 , wherein a circulating concentration of the non-acidified pharmaceutically acceptable nitrite salt is of 0.6 to 240 μM. 
     
     
         11 . The method of  claim 1 , wherein a circulating concentration of the non-acidified pharmaceutically acceptable nitrite salt is no more than about 100 μM. 
     
     
         12 . The method of  claim 1 , wherein a circulating concentration of the non-acidified pharmaceutically acceptable nitrite salt is no more than about 50 μM. 
     
     
         13 . The method of  claim 1 , wherein a circulating concentration of the non-acidified pharmaceutically acceptable nitrite salt is no more than about 20 μM. 
     
     
         14 . The method of  claim 1 , wherein said administering decreases blood pressure in the lungs of the subject, increases vasodilation or both. 
     
     
         15 . The method of  claim 1 , wherein said administering induces production in the subject of no more than about 25% methemoglobin. 
     
     
         16 . The method of  claim 1 , said administering induces production in the subject of no more than about 20% methemoglobin. 
     
     
         17 . The method of  claim 1 , said administering induces production in the subject of no more than about 15% methemoglobin. 
     
     
         18 . The method of  claim 1 , said administering induces production in the subject of no more than about 10% methemoglobin. 
     
     
         19 . The method of  claim 1 , said administering induces production in the subject of no more than about 5% methemoglobin. 
     
     
         20 . The method of  claim 1 , wherein the non-acidified pharmaceutically acceptable nitrite salt is administered with at least one additional agent 
     
     
         21 . The method of  claim 1 , wherein the subject is a human. 
     
     
         22 . The method of  claim 1 , wherein the subject further has a hemolytic condition and wherein said administering treats said hemolytic condition. 
     
     
         23 . The method of  claim 22 , wherein said hemolytic condition is sickle cell disease.