Effects of l-norgestrel on the endothelium-dependent relaxation response of rabbit clitoral cavernous smooth muscles

ObjectiveTo determine the effect of a popular oral contraceptive, l-norgestrel (a synthetic progestogen), on relaxing response of clitoral cavernous smooth muscles.DesignProspective, randomized study.SettingAcademic facility.Animal(s)Thirty adult female New Zealand White rabbits.Intervention(s)We conducted isometric tension studies with norepinephrine, endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators, and l-norgestrel. The effects of nonspecific nitric oxide synthase inhibitor (Nw-nitro-l-arginine methyl ester) and the potassium channel blockers (1 and 10 mM tetraethylammonium as well as 10 μM glibenclamide) on the reactivities of clitoral cavernous strips were investigated.Main Outcome Measure(s)Causation and power of developed tension after treatment.Result(s)Acetylcholine, sodium nitroprusside, and l-norgestrel produced concentration-dependent relaxation of the norepinephrine-precontracted strips. Both endothelium removal and treatment with 10 μM Nw-nitro-l-arginine methyl ester completely inhibited the relaxation response to acetylcholine and l-norgestrel, and supplementation with 10 mM l-arginine partially reversed the inhibition. Incubation with either tetraethylammonium (TEA) or glibenclamide reduced the l-norgestrel-induced relaxation in a dose-independent manner.Conclusion(s)The l-norgestrel–induced relaxation of the clitoral cavernous smooth muscle is endothelium and nitric oxide dependent and may be related to more than two types of potassium channels activation.