For several decades nitroglycerin has been administered to humans as a vasodilating agent in the treatment of cardiovascular disease. Recently, it has been shown that nitroglycerin so administered is converted in the body to nitric oxide which is the pharmacologically active metabolite. Still more recently, nitric oxide has been shown to be formed from arginine as a normal metabolite which is an important component of endothelium-derived relaxing factors (EDRF's). EDRF's are currently being intensively studied as participating in regulation of blood flow and vascular resistance. Incident to such study, a search has been carried out for compounds which block nitric oxide production in the body. The compound discovered for use to obtain this effect is N.sup.G -methyl-L-arginine (Palmer, R. M. J., et al, Nature (London), 333, pp. 664-666, 1988). Administration of N.sup.G -methyl-L-arginine to guinea pigs and rabbits has been shown to increase blood pressure (Aisaka, K., et al, Biochemical and Biophysic Research Communications, Vol. 160, No. 2, pp. 881-886, 4/28/89; Rees, D. D., et al, Proc. Natl. Acad. Sci. USA, Vol. 86, pp. 3375-3378, 5/89).
In addition to vascular endothelium, macrophages have also been shown to produce nitric oxide in the body which is a component of their cell killing and/or cytostatic function (Iyengar, R., et al, Proc. Natl. Acad. Sci, USA, Vol. 84, pp. 6369-6373, 9/87).
USPTO Backgrounds
USPTO Backgrounds