Supplemention with tetrahydrobiopterin suppresses the development of hypertension in spontaneously hypertensive rats

It has been suggested that tetrahydrobiopterin (H4B), a cofactor of NO synt hase, can reverse endothelial dysfunction caused by cardiovascular diseases , including atherosclerosis, coronary artery disease, and hypertension. Mor eover, an impairment of H4B biosynthesis in spontaneously hypertensive rats (SHR) was observed. Thus, we hypothesized that the defect of the H4B synth esis system may play an important role in the development of hypertension i n SHR. In the present study H4B (10 mg/kg per day IP) was used to treat SHR and Wistar-Kyoto rats (WKY) from the age of 5 through 16 weeks. Results de monstrated that chronic treatment with H4B significantly improved the impai red vascular responses to acetylcholine and suppressed the development of h ypertension in SHR but did not affect WKY. The increase of inducible NO syn thase expression, nitrotyrosine immunostaining, NO production, and superoxi de anion formation in adult SHR were also significantly suppressed by chron ic treatment with H4B. In contrast, H4B had no effect on WKY. In conclusion , this study demonstrated that H4B significantly attenuated the development of hypertension in SHR. The antihypertensive effect of H4B might be mediat ed through its direct antioxidant activity and/or decreasing oxygen free ra dical production from NO synthase, thereby reducing inducible NO synthase e xpression and peroxynitrite formation. Thus, the present study proposed tha t supplementation with H4B might be beneficial in preventing pathological c onditions such as essential hypertension.