Methods and compositions for the treatment of hypotension with arginine

Abstract

Methods and compositions for treating and inhibiting hypotension are provided. A therapeutic regimen useful in the present invention includes an arginine-free parenteral formulation administered concurrently with or followed by an arginine analog. The combination therapy provides an augmentation of the anti-hypotensive effect found by the present inventors with arginine analogs, such as N.sup..omega. -methyl-L-arginine, N.sup..omega. -amino-L-arginine or N.sup..omega. -nitro-L-arginine. These arginine analogs, otherwise described as nitric oxide synthase inhibitors, provide for a decrease in nitric oxide concentrations, and are demonstrated to elicit an increase in blood pressure in vivo, particularly in animals with cytokine and/or endotoxin induced hypotension. The parenteral formulation of the therapeutic regimen and methods of the invention are arginine-free and provide a decrease in plasma arginine levels. Reduced plasma and tissue levels of arginine in the animal function to augment the hypertensive action of arginine analogs to be administered concurrently or subsequent to administration of the parenteral formulation. This method provides a regiment for treating and/or inhibiting hypotension attendant a variety of conditions, including chemotherapeutic agent therapy (i.e., IFN, TNF), septic shock, trauma, exposure to endotoxins or cytokines, or other condition in which hypotension is attendant. The arginine-free formulations may also include ornithine, citrulline, or both.