Antioxidant effects of phosphodiesterase-5 inhibitors: reply

We thank Dr. Tanus-Santos for his interest in our study.1 The study by Muniz et al.2 found that erectile dysfunction patients with the lowest levels of endogenous nitric oxide (NO) have the best responses to the phosphodiesterase-5 (PDE5) inhibitor sildenafil. We believe an equivalent situation exists in patients with pulmonary arterial hypertension (PAH). We found impaired NO production in the patients with PAH included in our study, suggesting that these patients are the best candidates to take advantage of the benefits of vardenafil treatment. This may be because vardenafil is a relatively selective pulmonary vasodilator, which exerts its effect on PAH by increasing levels of cyclic guanosine monophosphate (cGMP) and augmenting the NO-cGMP axis. Monocrotaline (MCT)-induced PAH in rats may not fully represent PAH in humans; however, it is a well-established experimental model that has been extensively used.3 In our study, pathological alterations due to PAH became apparent 7 days after injection and thereafter progressively developed, leading to death ∼4 weeks later. Vardenafil treatment not only improved survival, but also reduced the severity of PAH. Similar results were shown in the study by Schermuly et al.4; the survival rate of the MCT group decreased gradually to 48% at Day 42, but fewer animals died in the MCT-sildenafil group when compared with the MCT group [survival rates: 70% (14/20) vs. 48% (12/25), respectively]. Vardenafil studies involving other animal models of PAH as well as in vivo and in vitro studies of related biochemical pathways that might be involved in PAH would be beneficial.