Effect of chronic lithium administration on endothelium-dependent relaxation of rat corpus cavernosum: the role of nitric oxide and cyclooxygenase pathways.
OBJECTIVE
To verify the effect of chronic lithium administration on the endothelium-dependent relaxation of rat corpus cavernosum, as lithium is a major drug for treating bipolar disorder and some studies showed that lithium might cause erectile dysfunction in such patients, by a mechanism as yet unknown.


METHODS
LiCl (600 mg/L) was dissolved in drinking water and Sprague-Dawley rats received the solution for 30 days; control rats received tap water. After 30 days corporeal strips were prepared from both groups, mounted under tension in oxygenated organ baths, and pre-contracted with phenylephrine (7.5 microm). After equilibration, the strips were relaxed by acetylcholine (10 nm to 1 mm) in the presence or absence of indomethacin (a cyclooxygenase inhibitor; 20 microm). Furthermore, the relaxant responses to sodium nitroprusside (1 nm to 1 mm), a nitric oxide (NO) donor, were investigated in both groups. NADPH-diaphorase histochemistry was used to identify NO synthase within cavernosal tissue strips of both groups.


RESULTS
The acetylcholine-dependent relaxation was significantly lower in lithium-treated rats than in controls. Although indomethacin decreased significantly the relaxant responses to acetylcholine in controls, it increased the relaxant responses in lithium-treated rats. NADPH-diaphorase staining was greater in the chronic lithium-treated than in control preparations. Sodium nitroprusside produced similar relaxation in both groups.


CONCLUSIONS
Chronic lithium administration can impair the endothelium-dependent relaxation of rat corpus cavernosum; NO availability might decrease after lithium administration and the cyclooxygenase pathways might have a role in this effect.
Sadeghipour
Hamed
H
Department of Pharmacology, School of Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Ghasemi
Mehdi
M
Nobakht
Maliheh
M
Ebrahimi
Farzad
F
Dehpour
Ahmad Reza
AR
D000818:Animals; D018692:Antimanic Agents / Q000009:adverse effects*; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D018783:Impotence, Vasculogenic / Q000139:chemically induced*; D018021:Lithium Chloride / Q000009:adverse effects*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018692:Antimanic Agents; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D018021:Lithium Chloride