Pulmonary hypertension (PH) is common in idiopathic pulmonary fibrosis (IPF) and is associated with systemic endothelial dysfunction. C21, currently in clinical development for IPF, is known to release nitric oxide (NO) from human endothelial cells in vitro, and the current phase 1 trial was conducted to explore effects of C21 on endothelial function in human subjects by measuring forearm blood flow (FBF). 
FBF was measured by strain-gauge venous occlusion plethysmography in 5 healthy male subjects after intra-arterial infusion of small, increasing doses of the ATRAG C21 at 3, 10, 30, 100, and 200 ?g/min infused sequentially in the forearm. Safety assessments (blood pressure, pulse, ECG, and safety laboratory parameters) were performed prior to and following administration of C21.
Compared to baseline, C21 increased the mean FBF up to 63% at the highest dose of 200 ?g/min (p=0.026) without effects on systemic blood pressure or any other side effects.
In conclusion, the results of this clinical trial showed an increase in FBF after intra-arterial infusion of C21, suggesting that ATRAGs may be useful in conditions with endothelial dysfunction. Moreover, measurement of FBF using strain-gauge venous occlusion plethysmography was shown to be a useful method for exploring vascular effects of ATRAGs and can be used for early clinical concept testing.