Aromatic-cationic peptides and methods for using same

Abstract

The present disclosure provides methods of preventing or treating renal ischemia-reperfusion injury in a mammalian subject and methods for chronic treatment of ARVD, including administering an effective amount of an aromatic-cationic peptide to a subject in need thereof. The methods include administering aromatic-cationic peptides to prevent or treat renal injury during the treatment of renal artery stenosis. The methods include administering an effective amount of an aromatic-cationic peptide to subjects in need thereof.

1 .- 83 . (canceled) 
     
     
         84 . A method for therapeutic treatment of atherosclerotic renal artery stenosis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a peptide D-Arg-2′,6′-Dmt-Lys-Phe-NH 2  or a pharmaceutically acceptable salt thereof, and further comprising the step of performing a revascularization procedure on the subject, wherein the revascularization procedure comprises the administration of one or more antihypertensive agents selected from the group consisting of diuretics, adrenergic receptor antagonists, calcium channel blockers, renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, aldosterone antagonists, vasodilators, and alpha-2 agonists. 
     
     
         85 . The method of  claim 84 , wherein the diuretics comprise loop diuretics, thiazide diuretics, thiazide-like diuretics, or potassium-sparing diuretics, or wherein the adrenergic receptor antagonists comprise beta blockers, alpha blockers, or mixed alpha and beta blockers. 
     
     
         86 . The method of  claim 84 , wherein the calcium channel blockers comprise dihydropyridines or non-dihydropyridines, or wherein the renin inhibitors comprise Aliskiren®. 
     
     
         87 . The method of  claim 84 , wherein the angiotensin converting enzyme (ACE) inhibitors comprise captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril, or benazepril. 
     
     
         88 . The method of  claim 84 , wherein angiotensin II receptor antagonists comprise Irbesartan®. 
     
     
         89 . The method of  claim 84 , wherein the aldosterone antagonists comprise eplerenone or spironolactone. 
     
     
         90 . The method of  claim 84 , wherein the vasodilators comprise sodium nitroprusside or hydralazine. 
     
     
         91 . The method of  claim 84 , wherein the alpha-2 agonists comprise clonidine, guanabenz, methyldopa, moxonidine, guanethidine, or reserpine. 
     
     
         92 . A method for improving vascular reactivity in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a peptide D-Arg-2′,6′-Dmt-Lys-Phe-NH 2  or a pharmaceutically acceptable salt thereof. 
     
     
         93 . The method of  claim 92 , wherein the subject is diagnosed with atherosclerotic renovascular disease (ARVD). 
     
     
         94 . The method of  claim 93 , wherein the ARVD comprises reduced renal blood flow (RBF) as compared to a normal control subject. 
     
     
         95 . The method of  claim 93 , wherein the ARVD comprises reduced glomerular filtration rate (GFR) as compared to a normal control subject. 
     
     
         96 . The method of  claim 92 , further comprising the step of performing a revascularization procedure on the subject. 
     
     
         97 . The method of  claim 96 , wherein the revascularization procedure comprises percutaneous transluminal renal angioplasty. 
     
     
         98 . The method of  claim 96 , wherein the subject is administered the peptide prior to the revascularization procedure, after the revascularization procedure, during and after the revascularization procedure or continuously before, during, and after the revascularization procedure. 
     
     
         99 . The method of  claim 98 , wherein the subject is administered the peptide for at least 3 hours after the revascularization procedure, for at least 5 hours after the revascularization procedure, for at least 8 hours after the revascularization procedure, for at least 12 hours after the revascularization procedure, or for at least 24 hours after the revascularization procedure. 
     
     
         100 . The method of  claim 98 , wherein the subject is administered the peptide starting at least 8 hours before the revascularization procedure, starting at least 4 hours before the revascularization procedure, starting at least 2 hours before the revascularization procedure, starting at least 1 hour before the revascularization procedure, or starting at least 10 minutes before the revascularization procedure. 
     
     
         101 . The method of  claim 96 , wherein the revascularization procedure comprises removal of a renal artery occlusion. 
     
     
         102 . The method of  claim 96 , wherein the revascularization procedure comprises administration of one or more thrombolytic agents. 
     
     
         103 . The method of  claim 102 , wherein the one or more thrombolytic agents are selected from the group consisting of: tissue plasminogen activator, urokinase, prourokinase, streptokinase, acylated form of plasminogen, acylated form of plasmin, and acylated streptokinase-plasminogen complex.