Blocking induction of tetrahydrobiopterin to block induction of nitric oxide synthesis

A method of prophylaxis or treatment of a subject for systemic hypotension caused by pathological overproduction of nitric oxide from arginine induced in vascular smooth muscle cells in said subject by therapy of said subject with a cytokine, said method comprising administering to said subject of therapeutically effective amounts of at least one guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist which is a reduced pterin that is a substrate for the pterin salvage pathway and of at least one dihydrofolate reductase inhibitor, thereby to inhibit nitric oxide synthesis in said cells to ameliorate said hypotension, said guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist which is a reduced pterin that is a substrate for the pterin salvage pathway being selected from the group consisting of 7,8-dihydro-L-biopterin and L-sepiapterin.

A method of treatment of a subject for systemic hypotension or expected systemic hypotension caused by pathological overproduction of nitric oxide from arginine induced in vascular smooth muscle cells in said subject by bacterial endotoxins, said method comprising administering to said subject of a therapeutically effective amount of (a) at least one guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist which is not a reduced pterin that is a substrate for the pterin salvage pathway or (b) at least one dihydrofolate reductase inhibitor or both (a) and (b), thereby to inhibit nitric oxide synthesis in said cells to ameliorate said hypotension.

A method of treatment of a subject for systemic hypotension or expected systemic hypotension caused by pathological overproduction of nitric oxide from arginine induced in vascular smooth muscle cells in said subject by bacterial endotoxins, said method comprising administering to said subject of therapeutically effective amounts of at least one guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist which is a reduced pterin that is a substrate for the pterin salvage pathway and of at least one dihydrofolate reductase inhibitor, thereby to inhibit nitric oxide synthesis in said cells to ameliorate said hypotension, said guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist which is a reduced pterin that is a substrate for the pterin salvage pathway being selected from the group consisting of 7,8-dihydro-L-biopterin and L-sepiapterin.