Possible Interaction: Arginine and Tetrahydrobiopterin

“BH4, L-arginine, or BH4 plus L-arginine inhibited eNOS monomerization.”

“In the presence of both l-arginine and tetrahydrobiopterin , eNOS is highly coupled (>90%), and the measured stoichiometry of O2/NADPH is very close to the theoretical value.”

“Inhibition and reconstitution of pteridine synthesis in activated murine macrophages by specific drugs demonstrate that tetrahydrobiopterin regulates the amount of nitrogen oxides formed from arginine in intact cells, thus providing a rationale for therapeutic intervention.”

“This cofactor is absolutely required for all aromatic amino acid hydroxylations, and, recently, nitric oxide production from L-arginine has also been found to be dependent on tetrahydrobiopterin.”

“In the ischemic hindlimb, cosupplementation with BH4 + L-arginine resulted in greater eNOS and phospho-eNOS (P-eNOS) expression, Ca2+-dependent NOS activity and NO concentration in the ischemic calf region (gastrocnemius), as well as greater NO concentration in the region of collateral arteries (gracilis).”

“Rats receiving cosupplementation of BH4 + L-arginine led to greater recovery of foot perfusion and greater collateral enlargement than did rats receiving either agent separately.”

“Cosupplementation with BH4 + L-arginine resulted in greater eNOS expression, Ca2+-dependent NOS activity and NO concentration in gastrocnemius from the ischemic hindlimb, as well as greater recovery of foot perfusion and more collateral artery enlargement than did rats receiving either agent separately.”

“Thirdly, tetrahydrobiopterin enhances cardiomyocyte NO synthesis by augmenting l-arginine uptake, presumably by modulating CAT-2A expression (Schwartz et al. 2001).”

“Pretreatment with BH4 (10-5 M) enhanced the vasodilator responses to L-Arg in the Ovx group compared with the untreated Ovx group.”

“ L-arginine and tetrahydrobiopterin administration both resulted in a significant preservation of tissue NO concentrations and an improvement in LDF, compared to control animals given saline.”

“It is concluded that (a) BH4 does not regulate the intracellular concentration of …) less binding of BH4 to NOS occurs in BH4 deficiency states; (c) BH4 has a potent effect … of NOS for arginine ; and (d) the availability of arginine for NOS … become severely limiting in BH4 deficiency states.”