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Arginase Inhibitors and Erectile Dysfunction

Most men know that L-Arginine plays a role in the production of erectile strength-promoting nitric oxide, something I cover in my link on The Failures and Successes of Arginine. Viagra and Cialis works on an enzyme called NOS (Nitric Oxide Synthase) and, of course, has been quite effective.  So why would going farther upstream and targeting arginase help? The reason is simple:  NO synthase and arginase compete for the same substrate (L-arginine). [1]

NOTE:  It is arginase II that is actually involved in endothelial dysfunction.

"Since NO synthase and arginase compete for the same substrate (L-arginine), over-expressed arginase can affect NO synthase activity and NO-dependent smooth muscle relaxation by depleting the substrate pool of L-arginine that would otherwise be available to NO synthase." [1]

Around a decade ago, researchers began to speculate that arginase inhibitors could be used to improve erectile function. One 2004, study, for example, wrote that "We present data to suggest that arginase may regulate NO production by competing for endogenous pools of L-arginine. In this fashion, arginase is an indirect regulator of penile and vaginal blood flow and specific arginase inhibitors may improve genital blood flow during sexual arousal." [2] Notice that they said "may" and so, basically, this was a feasability study with a call to action. Subsequent animal studies showed that endothelial function was improved with arginase inhibitors but none studied erectile tissues as far as I know.

This was addressed in 2009 when a study examined in vitro the effects of four arginase inhibitors on human penile erectile tissues from the corpus cavernosum.  Their results were lackluster and the authors concluded that "arginase inhibitors appeared to be ineffective in reversing the adrenergic tension and increasing the electrically induced relaxation of isolated HCC." [3] Therefore, it would appear that these are probably not going to be the next "big gun" in the fight against erectile dysfunction.

So more research needs to be done, but early results do not appear to be promising.  In addition, I have not been able to find any legal, approved arginase inhibitors.  There is nor-NOHA, which is available commerically.  One supplier is very clear that "this product is not for human or veterinary use."

However, arginase inhibitors are likely to be forthcoming due to an interesting application:  protecting diabetics from heart and arterial disease.  Diabetics simply do not respond to normal cardiovascular interventions and scientist recently found out why:  diabetics have elevated arginase levels. [5] Several lines of evidence point to this being a root cause issue for many of the debilitating effects of diabetes and arginase inhibitors look promising.

However, at this point, I do not see any physicians using arginase inhibitors for treatment of erectile dysfunction.

 

REFERENCES::

1)  Nitric Oxide. 1999 Dec, 3(6):427-38, "Effects of the new arginase inhibitor N(omega)-hydroxy-nor-L-arginine on NO synthase activity in murine macrophages"

2) Nutr, 2004 Oct, 134(10 Suppl):2873S-2879S; "Role of arginase in the male and female sexual arousal response"

3) World J Urol, 2009 Dec, 27(6):805-10, "Effects of arginase inhibitors on the contractile and relaxant responses of isolated human penile erectile tissue"

4) Br J Pharmacol, 2009 January, 156(1):84–93, "The vascular effects of different arginase inhibitors in rat isolated aorta and mesenteric arteries"

5) http://www.emaxhealth.com/1020/arginase-inhibitors-might-prevent-diabetic-heart-disease

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