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

Abstract

Objective: To determine the effect of a popular oral contraceptive, L-norgestrel (a synthetic progestogen), on relaxing response of clitoral cavernous smooth muscles. Design: Prospective, randomized study. Setting: Academic 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 (N-w-nitro-L-arginine methyl ester) and the potassium channel blockers (1 and 10 mM tetraethylammonium as well as 10 mu M 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 mu M N-w-nitro-L-arginine methyl ester completely inhibited the relaxation response to acetlycholine 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.