Platelets, oxidant stress and erectile dysfunction: an hypothesis.

Abstract

Time for primary review 30 days. The successful use of sildenafil (Viagra™) to treat vasculogenic erectile dysfunction (VED) has heightened awareness of the widespread prevalence of this disorder [1–3]. Sildenafil acts through the augmentation of nitric oxide (NO) actions on vascular/corpus cavernosal smooth muscle cell relaxation [1–4] (Fig. 1). Thus, the therapeutic use of sildenafil has also highlighted the central role played by NO in mediating normal erection and in the pathogenesis of VED. Nevertheless, we still know little about the basic pathophysiology of VED. Since prevention is preferable to cure, it is imperative to improve our understanding of the pathophysiology of VED. In this brief review, we suggest that another major consequence of diminished NO formation is the increased adhesion of platelets and leukocytes, in particular neutrophils, which may counter erection through release of vasconstrictors, superoxide and other oxygen free radicals. We also suggest that erection itself may trigger events that contribute to exacerbation of the disorder in the long-term, again through the adhesion of platelets and leukocytes. Fig. 1 Key events in normal penile erection — the central role of NO. Upon sexual arousal, sympathetic drive initiates erection through both sympathetic and non-adrenergic, non-cholinergic (NANC) innervation of the corpus cavernosum and pudendal arteries. NANC fibres release NO and acetylcholine stimulates the release of NO from local endothelium by activation of NO synthase (NOS). NO promotes relaxation of arterial and cavernosal smooth muscle through activation of guanylate cyclase and suppression of activator Ca2+ which in turn results in erection. It is now well established that impairment of the above systems is central to the aetiology of vasculopathic erectile dysfunction. Sildenafil promotes erection through inhibition of type V phosphodiesterase which blocks the metabolism of cGMP to inactive GMP. Thus, cGMP accumulates thereby promoting relaxation of the relevant VSMCs. Patients with … * Corresponding author. Tel.: +44-117-928-3154; fax: +44-117-929-9737 j.y.jeremy{at}bristol.ac.uk