S. Gur, P.J. Kadowitz, and W.J. Hellstrom, Department of Urology, Tulane Health Sciences Center, New Orleans, Louisiana
 70112, USA, J Urol. 2007 Oct;178(4 Pt 1):1543-8. Epub 2007 Aug 16.

 PURPOSE:

           We investigated the relaxant effects of repetitive administration of L-arginine, the substrate for nitric oxide, at hourly intervals and
 elucidated its mechanism of action in human corpus cavernosum. MATERIALS AND METHODS: Samples of human corpus cavernosum
 were suspended in an organ chamber for measurements of isometric tension. After precontraction with phenylephrine (10 microM),
 concentration-response curves were performed for L-arginine at 2-hour intervals (1 to 10 hours). Underlying mechanisms of relaxation
 were evaluated by inhibitory and stimulatory agents. RESULTS: After a brief incubation period of 1 to 4 hours L-arginine (0.1 to 1,000
 microM) but not D-arginine induced minor changes in HCC. In contrast, when incubation time was increased to 6 to 10 hours L-arginine
 evoked detectable human corpus cavernosum relaxation proportional to concentration and time. Relaxation was significantly attenuated by
 the nitric oxide synthase inhibitor L-NAME, the blocker of soluble guanylyl cyclase ODQ and the blocker of small conductance Ca2+
 activated K+ channels apamin, and partially by the inducible nitric oxide synthase inhibitor aminoguanidine and the cyclic guanosine 5'-
 monophosphate dependent protein kinase G inhibitor Rp-8-pCPT-cGMPS. Relaxation was potentiated in the presence of the membrane
 permeable cyclic guanosine 5'- monophosphate analogue 8-bromo-cyclic guanosine 5'-monophosphate, the Rho-kinase inhibitor Y-27632
 and the phosphodiesterase-5 inhibitor sildenafil. CONCLUSIONS: These observations demonstrate that L-arginine induces
 slow and prolonged relaxation of human corpus cavernosum. This may occur by restoring the endogenous amino acid pool for nitric
 oxide synthesis and by nitric oxide-soluble guanylyl cyclase-protein kinase G signaling involving the activation of KCa channels or by
 inhibiting the up-regulated RhoA/Rho-kinase pathway. The use of sildenafil combined with L-arginine further facilitates erections
 and it may benefit men with more severe erectile dysfunction.

 PMID: 10849504 [PubMed - indexed for MEDLINE]