Viagra: The Little Blue Wonder Pill

If you’ve ever watched TV, I’m sure you have heard the all too familiar, “Why let erectile dysfunction get in your way. Talk to your doctor about Viagra today; 21 million men already have.” Viagra, Sildenafil, works to enhance the erectile response in sexually stimulated males. As we learned in class, a male must be under parasympathetic nervous system control to allow increased blood flow to the penis, but how does this work? When a male becomes sexually aroused, nitric oxide (NO) is released within the penis, stimulating the production of the messenger cyclic guanosine monophosphate (cGMP), which causes relaxation of smooth muscles (1). Arteries of the penis then dilate, allowing for increased blood flow, and ultimately engorgement, an erection. Sildenafil helps in erectile dysfunction, because it maintains cGMP levels within the smooth muscles. Sildenafil’s affect on cGMP level is an important characteristic that has been continually used to find new treatment options for a variety of medical problems.

As if helping erectile dysfunction was not enough, Mitschke et al. found that Sildenafil, through the actions of cGMP, can promote weight loss in mice (3). Sildenafil was shown to increase browning of white adipose tissue, which occurs when white adipose tissue takes on phenotypic characteristics of brown fat cells. White adipose tissue (WAT) serves as a place of triglyceride storage, whereas brown adipose tissue (BAT) metabolizes fatty acids to release energy as heat. Inducing browning of WAT could ultimately allow weight loss, since an increased ratio of BAT to WAT would promote increased energy expenditure. This weight loss potential of Sildenafil is a promising discovery for the treatment of obesity.

Interestingly, Sildenafil has also been shown to reverse the symptoms of nephrogenic diabetes insipidus (release of large quantities of dilute urine), and has been used in the treatment of pulmonary hypertension in pregnant women (2,4). Sildenafil’s affect on cGMP level is the key to such treatments. The role of cGMP in many different areas of the body supports the importance of second messenger systems we have studied in class.

1. British Pregnancy Advisory Service. (2010). Viagra (Sildenafil) Facts [Online]. BPAS. http://www.bpas.org/bpasman/Viagra [27 Oct. 2013].

2. Maharaj CH, O’Toole D, Lynch T, Carney J, Jarman J, Higgins BD, Morrison JJ, Laffey JG. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries. Reproductive Biology Endocrinology 7: 34, 2009.

3. Mitschke MM, Hoffmann LS, Gnad T, Scholz D, Kruithoff K, Mayer P, Haas B, Sassmann A, Pfeifer A, Kilic A. Increased cGMP promotes healthy expansion and browning of white adipose tissue. The FASEB Journal 27(4): 1621-1630, 2013.

4. Sanches TR, Volpini RA, Shimizu MHM, de Braganca AC, Oshiro-Monreal F, Seguro AC, Andrade L. Sildenafil reduces polyuria in rats with lithium-induced NDI. American Journal of Physiology Renal Physiology 302: F216-F225, 2012.