Tetrahydrobiopterin (BH4), a Cofactor for nNOS, Restores Gastric Emptying and nNOS Expression in Female Diabetic Rats

摘要: Gastroparesis is a debilitating disease predominantly affecting young women. Recently, dysregulation of neuronal nitric oxide synthase (nNOS) in myenteric plexus neurons has been implicated for delayed solid gastric emptying/gastroparesis diabetic patients. In this study, we have explored the role tetrahydrobiopterin (BH4), major cofactor nNOS activity and NO synthesis gastroparesis. Diabetes was induced with single injection streptozotocin (55 mg/kg body wt, ip) female rats, experiments performed on week 3 or 9 following induction, without 3-wk BH4 supplementation. Gastric pyloric levels were significantly decreased rats compared control (18.6 ± 1.45 vs. 31.0 2.31 pmol/mg protein). vitro studies showed that 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor synthesis, release nitrergic relaxation. Three-week dietary supplementation either from day 1 6 attenuated diabetes-induced emptying solids (3 wk: BH4, 67 6.7 diabetic, 36.05 7.09; 57 8.45 33 9.91) reduction nNOS-α protein expression rats. Supplementation restored dimerization 9-wk-old addition, treatment reversed (17.23 5.81 42.0 2.70 mmHg × s) changes intragastric pressures (IGP) relaxation (−0.62 0.01 −0.22 0.07). deficiency plays critical alterations including emptying, increased IGP, reduced relaxation, accelerates by restoring system Therefore, potential therapeutic option patients