NITRIC OXIDE SYNTHESIS INHIBITORS FOR POTENTIATING THE ACTION OF PRESSOR AGENTS IN CERTAIN HYPOTENSIVE PATIENTS

摘要

A method for treatment of an animal for systemic hypotension induced by internal nitric oxide production caused by endotoxin or cytokines. The method involves administering an alpha 1 adrenergic agonist and an amount of an inhibitor of nitric oxide formation from arginine to restore vascular contractile sensitivity to alpha 1 adrenergic agonists. A preferred inhibitor of nitric oxide formation is an NG-substituted arginine having at least one hydrogen on a guanidino amino group replaced by another atomic or molecular species, including NG-aminoarginine, NG-nitroarginine, and NG-alkylarginines such as NG-methylarginine, NG-ethylarginine, NG-propylarginine and NG-butylarginine. Arginine derivative inhibitors are preferably of the L configuration and include pharmaceutically acceptable addition salts. Treatment of systemic hypotension in a patient which has been induced by chemotherapy with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be likewise accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, or other bacterial toxins, e.g., septic shock, may also be accomplished by treatment with alpha 1 adrenergic agonists and an inhibitor such as an arginine derivative, restoring vascular contractile sensitivity to the alpha 1 adrenergic agonists.