EFFECTS OF LONG-TERM ORAL-ADMINISTRATION OF L-ARGININE ON THE RAT ERECTILE RESPONSE

Purpose: Nitric oxide (NO), the neurotransmitter responsible for media ting penile erection in the rat, is synthesized from L arginine by nit ric oxide synthase (NOS) in a reaction blocked by L-NAME (N-Omega-nitr o-L-arginine methyl ester). To determine whether dietary supplementati on of L-arginine can stimulate penile erection and whether ancillary p athways for penile erection may exist, a series of experiments were co nducted in the Fischer 344 rat, Materials and Methods: Adult male (5 m onth old) and aged (20 month old) rats were fed L-arginine (2.25%) and L-NAME (0.7%) dissolved in tap water for 8 weeks. Animals (n = 6) und erwent electrical field stimulation (EFS) of the cavernosal nerve to i nduce erection and both maximal intracavernosal pressure (MIP) and mea n arterial pressure (MAP, mm, Hg +/- SEM) were measured. Tissue and se rum levels of L-arginine were measured by an automated amino acid anal yzer, Penile eNOS (endothelial) and nNOS (neuronal) content were measu red by western blot densitometry, Total penile NOS enzyme activity was measured by the L-arginine to L-citrulline conversion assay. Results: The L-arginine fed animals demonstrated a significant increase in EFS -induced MIP when compared to the controls in both the adult (104 +/- 4 vs. 86 +/- 6, p = 0.04) and aged (87 +/- 5 vs, 66 +/- 4, p = 0.02) a nimals, without changes in MAP. L-NAME virtually abolished the MIP in adult rats (8 +/- 3, p < 0.0001), while increasing the MAP (186 +/- 8, p < 0.0001), Serum and penile tissue levels of L-arginine were increa sed by 64-148% in all groups compared to control animals. Penile eNOS and nNOS content remained unchanged in control and treated animals, Pe nile NOS activity was increased nearly 100% in the L-arginine treated groups vs, controls, Conclusions: Long-term oral administration of sup ra-physiologic doses of L-arginine improves the erectile response in t he aging rat. We postulate that L-arginine in the penis may be a subst rate-limiting factor for NOS activity and that L-arginine may up-regul ate penile NOS activity but not its expression. The blockade of penile erection by EFS with L NAME suggests that if ancillary corporeal vaso dilator mechanisms develop, a basal level of NO synthesis is still req uired for activation and relaxation of the corporeal smooth muscle. Th ese data support the possible use of dietary supplements for treatment of erectile dysfunction.