We did not measure BH4 or dihydrobiopterin (BH2) levels, but the literature provides some insight into the mechanisms implicated in the beneficial effects of BH4. For example, in a murine model of renal ischemia, Kakoki et al2 reported that BH4 administration restored the NO levels that had been decreased by renal ischemia. Moreover, the dimeric form of endothelial NO synthase decreased in the ischemic kidney and was restored by BH4. In that model, BH4 administration also restored endothelium-dependent vasodilation mediated by NO release.2
Numerous studies, including studies on humans, have shown that BH4 administration can improve vascular function in different settings, including in microvascular skeletal muscle and the coronary microcirculation, in hypercholesterolemia and during septic shock.3–5
Our results6 are in line with these observations and further add that BH4 protects the kidney from ischemia–reperfusion via microvascular and cellular mechanisms independent of its systemic effects.