Leptin Enhances Nitric Oxide-Dependent Relaxation of the Clitoral Corpus Cavernosum

PURPOSE The effects of leptin on female sexual behaviors are controversial, and studies on this topic are limited. The objectives of this study were to evaluate the direct effects of leptin on clitoral vasoreactivity in vitro and to determine the mechanism of action. MATERIALS AND METHODS Isometric tension studies were conducted to determine the effects of pretreatment with leptin (10(-8) M) on the contractile responses of rabbit clitoral corpus cavernosal smooth muscle strips. The effects of leptin were assessed on precontraction induced by phenylephrine (PE; 10(-9)-10(-4) M) and KCl (35-140 mM). We also examined the effect of leptin on relaxation induced by acetylcholine (ACh; 10(-9)-10(-4) M), verapamil (10(-10)-10(-6) M), and sodium nitroprusside (10(-9)-10(-4) M) in PE-precontracted (10(-5) M) strips. RESULTS Leptin enhanced ACh-induced relaxation in PE-precontracted strips. L-NAME pretreatment significantly reduced the effect of leptin on ACh-induced relaxation, whereas L-arginine potentiated the effect of leptin. Leptin decreased the KCl-induced contractile responses. Leptin increased verapamil-induced relaxation responses. The relaxation effects of leptin on KCl-induced contraction were inhibited by 10(-5) M methylene blue and L-NAME pretreatment. CONCLUSIONS A high concentration of leptin enhances ACh-dependent relaxation in clitoral cavernosal smooth muscles. These relaxation effects of leptin may occur through an NO-dependent mechanism and voltage-dependent calcium channel blockade.