PT - JOURNAL ARTICLE AU - Javier Angulo AU - Pedro Cuevas AU - Ignacio Moncada AU - Antonio Martín-Morales AU - Antonio Allona AU - Argentina Fernández AU - Sonia Gabancho AU - Peter Ney AU - Iñigo Sáenz de Tejada TI - Rationale for the Combination of PGE<sub>1</sub> and<em>S</em>-Nitroso-glutathione to Induce Relaxation of Human Penile Smooth Muscle DP - 2000 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 586--593 VI - 295 IP - 2 4099 - http://jpet.aspetjournals.org/content/295/2/586.short 4100 - http://jpet.aspetjournals.org/content/295/2/586.full SO - J Pharmacol Exp Ther2000 Nov 01; 295 AB - Many men with erectile dysfunction have been successfully treated with intracavernosal injection of prostaglandin E1(PGE1) but this treatment is ineffective in 30 to 40% of patients. The goals of this study were to characterize PGE1-induced relaxation of isolated human penile smooth muscle (penile arteries and trabecular strips), correlating this in vitro response with the clinical response to this drug, and to evaluate the effects of the combination of PGE1 withS-nitrosoglutathione (SNO-Glu) on relaxation of isolated human penile smooth muscle. Large variability in the EC50and maximal relaxation induced by PGE1 was observed between tissues of different patients. Patients with poor clinical response to intracavernosal alprostadil (PGE1) had significantly larger EC50 values and smaller maximal relaxation compared with patients with partial or complete clinical response to this drug. SNO-Glu consistently produced complete or near complete relaxation of human corpus cavernosum strips and penile arteries, even when the tissue responded poorly to PGE1. In trabecular strips, the combination of PGE1 and SNO-Glu in a 1:100 ratio demonstrated a synergistic relaxation effect. The combination of PGE1 and SNO-Glu simultaneously increased the levels of both cAMP and cGMP in human corpus cavernosum tissue. Our results suggest that the clinical effectiveness of intracavernosal administration of PGE1 is related to the variability of the relaxation responses of human trabecular tissue and penile arteries to this drug. The synergistic interaction of PGE1 and SNO-Glu makes this combination an effective method to cause penile smooth muscle relaxation, a necessary step to initiate and maintain penile erection. The American Society for Pharmacology and Experimental Therapeutics