Sildenafil inhibition cGMP phosphodiesterase

NO-mediated synthesis of cGMP from GTP in the corpus cavernosum that leads to smooth muscle relaxation. Sildenafil potentiates the effects of NO by inhibiting cGMP phosphodiesterase. 

Involved in penile erection sildenafil citrate (Viagra) affects this process by inhibiting a cGMP phosphodiesterase... 

Figure 11.14. Stracture of sildenafil (Viagra ), and sketch of its mechanism of action Inhibition of phosphodiesterase increases cGMP levels.

The authors suggested that in this case the effect of sildenafil may have been reduced by impaired gastrointestinal absorption. They speculated that exogenous nitric oxide inhibits nitric oxide sjmthase activity, with a consequent reduction in pulmonary vascular smooth muscle cGMP concentration. Phosphodiesterase type V inhibitors, such as sildenafil, increase cGMP concentration and ameliorate the rebound effect... 

Sildenafil is a selective inhibitor of phosphodiesterase type-5 that is orally effective in the treatment of erectile dysfunction. Its pharmacological actions are a consequence of prolonging the signaling actions of NO because this drug prevents cGMP hydrolysis by inhibition of a cGMP phosphodiesterase V subtype enriched in penile smooth muscle (1, 10, 143). 

Figure 35.17 Muscle-relaxation pathway. Increases in NO levels stimulate guanylate cyclase, which produces cGMP. The increased cGMP concentration promotes smooth muscle relaxation. Phosphodiesterase 5 hydrolyzes cGMP, which lowers the cGMP concentration. The inhibition of phosphodiesterase 5 by sildenafil maintains elevated levels of cGMP.

Phosphodiesterase 5 (PDE5) is found in blood vessels supplying the corpora cavernosa. Sildenafil inhibits PDE 5 - T cGMP -> vasodilation - T blood flow ->T erectile response. If used concomitantly with nitrates or other potent vasodilators, the excessive fall in blood pressure may lead to death from cardiovascular causes, including myocardial infarct. 

Sildenafil (Viagra ), tadalafil (Cialis ), and vardenafil (Levitra ) act by selectively inhibiting phosphodiesterase (PDE) type 5, an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP, smooth muscle relaxation is... 

Sildenafil increases the release of nitric oxide and increases the levels of cyclic guanosine monophosphate (cGMP), a smooth muscle relaxant. Sildenafil enhances the effects of nitric oxide by inhibiting phosphodiesterase 5, an enzyme found primarily in the penis that degrades cGMP. As a result, increased levels of cGMP in the corpus cavemosum enhance smooth muscle relaxation, the inflow of blood, and erection. Sildenafil has no effect in the absence of sexual stimulation (see Figure 60.1). 

Sildenafil has recently been approved for treatment of PAH through its inhibition of cGMP and smooth muscle relaxation of the pulmonary vasculature. The reader is referred to the previous discussion of phosphodiesterase inhibitors under the topic of vasodilators. 

Since the discovery of sildenafil for the treatment of ED in 1993, two additional products, vardenafil and tadalafil, have been introduced to the market [6, 7]. All these three drugs work by inhibiting type 5 phosphodiesterase (PDE5). This inhibition increases the amount of cyclic guanosine monophosphosphate (cGMP), which... 

---