cGMP mediates corpus cavernosum smooth muscle relaxation with altered cross-bridge function.

We tested the prevailing paradigm that relaxation of corpus cavernosum smooth muscle (CCSM) and penile erection depends upon nitric oxide-induced elevation of myoplasmic cGMP and reduced Ca2+-dependent myosin regulatory light chain phosphorylation levels. This hypothesis invokes a reversal of normal activation pathways. Upon stimulation with 250 microM phenylephrine, phosphorylation of the 20 kD myosin regulatory light chains of rabbit or human CCSM increased approximately 4-fold coincident with contraction. Removal of the agonist was followed by a slow reduction in cross-bridge phosphorylation and force to basal levels. The NO donor, sodium nitroprusside elicited a dose-dependent increase in tissue [cGMP] associated with a rapid relaxation in the continued presence of phenylephrine, although cross-bridge phosphorylation remained significantly elevated. Thus the NO-cGMP inhibitory pathway in CCSM is not simply a reversal of excitatory signal transduction mechanisms. An unidentified mechanism contributes to relaxation by decreasing the rate of cross-bridge recruitment through phosphorylation.