Because the primary cause of early death (6–12 months of age) of TNF-Tg mice is pulmonary hypertension, which is also the primary toxicity associated with NO inhibitors [56], we speculate that the combined TNF-induced pathology and adverse drug effects lead to unacceptable side effects that preclude study of potent NOS inhibitors in this model. This evidence concerns the gene NOS2 and pulmonary hypertension.