Corpus cavemosum, smooth muscle relaxation

Ignarro, L. I, Bush, P. A., Buga, G. M., Wood, K. S., Fukuto, J. M., and Rajfer, J., 1990, Nitric oxide and cychc GMP formation upon electrical field stimulation cause relaxation of corpus cavemosum smooth muscle, Biochem. Biophys. Res. Commun. 170 843-850. 

In a series of studies conducted in our laboratory (Ignarro et al., 1990b Rajfer et al., 1992), relaxation of corpus cavemosum smooth muscle from the penis of the rabbit and human caused by electrical stimulation of the NANG neuronal pathway was found to be inhibited by oxyhemoglobin, methylene blue, N°-nitro-... 

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). 

The mechanism of action of tadalafil is similar to the other PDE5 inhibitors, sildenafil and vardenafil. Through the inhibition on PDE5, tadalafil increases the concentrations of cGMP, producing smooth muscle relaxation and increased blood flow to the corpus cavemosum, thereby enhancing erectile response following appropriate sexual stimulation [52-55]. 

The drug sildenafil, sold imder the trade name Viagra, is a potent inhibitor of phosphodiesterase V (PDE V), an enzyme found in high levels in the corpus cavemosum of the penis. Inhibitors of this enzyme enhance vascular smooth muscle relaxation and are used for treatment of male impotence. Following is an outline for a s)mthesis of sUdenafil. 

Uses Viagra ED, Revatio Pulm artery HTN Action X PDE5 (responsible for cGMP breakdown) T cGMP activity to relax smooth muscles T flow to corpus cavemosum and pulm vasculature antiproliferative on pulm artery smooth muscle Dose ED 25-100 mg PO 1 h before sexual activity, max 1 X d if >65 y avoid... 

Erection occurs as a result of increased pressure in the corpora cavernosa, which translates into penile rigidity. The pressure increase is caused by three synergistic processes (i) relaxation of the smooth muscles of the corpora cavernosa (2)increase in arterial blood flow to the penis and (5) restriction of the venous blood flow out of the penis. Both central and peripheral mechanisms contribute to the process of penile erection. At the central level, the psychological component of penile erection is controlled by the hypothalamic and limbic systems (140). At the peripheral level, both sympathetic and parasympathetic pathways as well as several mediators are involved. Psychogenic and local stimulation results in the release of neurotransmitters from the cavemosal nerve terminals and smooth muscle endothelium. Factors that mediate the corpus cavemosum relaxation include nitric oxide (NO), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), and prostaglandin. 

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