Nitric oxide (NO) mediates penile erection by inducing cavernosal smooth muscle relaxation. Superoxide anion (O2-) can influence the activity of NO by reacting with it to produce peroxynitrite (PN). This is a highly reactive species that is known to attack a variety of biological targets. It is far more reactive and damaging than its precursors. We therefore, investigated the effect of PN on rabbit cavernosal smooth muscle relaxation and compared it to NO. Cavernosal strips from nine adult New Zealand White rabbits were excised (n = 12 strips for each arm of the study) and mounted in organ baths. After pre-contraction with phenylephrine (PE) (100 microM) the strips were exposed to either NO or PN (1-100 microM) and subsequent smooth muscle relaxations monitored. Some tissues were incubated with oxadiazoloquinoxalin-1-one (ODQ; 10 microM), an inhibitor of guanylyl cyclase, before the addition of NO or PN. NO and PN induced concentration-dependent relaxations in all strips. However, PN (IC50: 26 +/- 3.6 microM) was significantly less potent than NO (IC50: 11 +/- 0.7 microM) [P < 0.01]. Relaxation induced by NO was immediate and short-lived, with the tension returning to its original level. In contrast, PN-initiated relaxations were of a slower onset and more prolonged, with the tissues unable to recover tension. However, after several washouts the tissues were fully responsive to PE. Both NO- and PN-mediated relaxations were inhibited by ODQ, suggesting the involvement of cGMP in this process. Although PN mediates cavernosal smooth muscle relaxation, it is much less potent than NO. As PN is thought to play a role in a variety of pathologies where erectile dysfunction is prominent, it may also contribute to the pathogenesis of erectile dysfunction.