Nitric Oxide Regulation of Penile Erection: Biology and Therapeutic Implications

For approximately a decade now, substantial evidence has accrued supporting nitric oxide (NO) as the central component of a major signal transduction system that acts in the penis to mediate the erectile response.This molecule subserves a unique biochemical cascade involving production of the potent second-messenger molecule, 3Ј, 5Јcyclic guanosine monophosphate (cGMP), and its activation of protein kinase G (PKG), which induces physiologic penile erection by regulating the state of penile smooth muscle contractility (Burnett, 1997).In fact, current data support the notion that this NO-based biochemical cascade represents a convergence of cellular, biochemical, and molecular inputs, which, on the signal transduction regulatory level, is indispensable for the mechanism of penile erection (Hedlund et al, 2000a).Consistent with the importance of NO mediation of penile erection, its biology in the penis is quite complex, involving multiple regulatory interactions: the molecule itself may target several biochemical mechanisms that achieve erectile tissue relaxation, but it is also the target of a host of modulatory influences that determine its release and mode of action in erectile tissue.At the same time, this premier signal transduction mechanism has been exploited for therapeutic purposes, specifically in the clinical management of erectile dysfunction.Discoveries pertaining to the field of NO biology in the penis have, in recent years, been rapidly translated into the clinical development of the first orally effective pharmacotherapy for erectile dysfunction, sildenafil citrate (Viagra) (Goldstein et al, 1998).This