Restoration of normal adult penile erectile response in aged rats by long-term treatment with androgens.
In order to determine whether the aging-related impairment of penile erection can be corrected by exogenous androgens, 20-mo-old ("old") rats received implants of Silastic tubing containing either testosterone (T) or dihydrotestosterone (DHT). Untreated aged-matched rats were used as reference controls, and values were compared with those obtained previously for 5-mo old ("adult") rats. After 45 days, groups of six rats were submitted to electrical field stimulation of the cavernosal nerve (EFS), and the intracavernosal pressure and mean arterial pressure (MAP) were recorded. Compared to the untreated old rats, the old animals receiving either T or DHT showed a similar and significant (p < 0.01) increase (56%) in the maximal intracavernosal pressure (MIP) to a level slightly above that of the untreated adult rats. The response was sensitive to the nitric oxide synthase (NOS) inhibitor Nw-nitro-L-arginine methyl ester (L-NAME). The MIP:MAP ratio in the treated animals was nearly double that found in the old untreated controls. Penile NOS activity was measured by the [3H]L-arginine-citrulline conversion, and neuronal NOS (nNOS) levels were estimated by a semiquantitative Western blot assay with antibodies against human nNOS. No significant variations were observed in either NOS levels or NOS activity between the treated and untreated old rats. These results suggest that aging-related erectile dysfunction in the intact rat may be responsive to androgen therapy and that this correction is not associated with an increase in the basal levels of penile NOS, in contrast to what occurs in castrated rats.
Garban
H
H
Department of Surgery, UCLA School of Medicine, Torrance 90509, USA.
Marquez
D
D
Cai
L
L
Rajfer
J
J
Gonzalez-Cadavid
N F
NF
D000375:Aging / Q000502:physiology*; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000494:pharmacology; D004343:Drug Implants; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000294:innervation / Q000502:physiology; D011312:Pressure; D051381:Rats; D011916:Rats, Inbred F344; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology
D000728:Androgens; D004343:Drug Implants; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D009569:Nitric Oxide; D013739:Testosterone; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester