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INTRODUCTION: Sexual dysfunction is significantly more prevalent in women than in men. However, to date, no satisfactory oral treatment is yet available. AIM: The aim of this study was to study the effects of adenosine monophosphate (AMP) alone or its combination with L-Arginine on the relaxation of the female rabbit corpus cavernosum. METHODS: Cylinder strips from the corporal body of the excised clitoris from female New Zealand White rabbits were incubated in Krebs solution. Phenylephrine (PE) precontraction was achieved, then the drugs AMP and L-Arginine were administered either independently or in sequential combinations to the strips under precontracted conditions. MAIN OUTCOME MEASURES: Contraction percentages were compared. RESULTS: When precontraction was induced by PE 8 µM or 20 µM, AMP was shown to induce relaxation up to 25% in a dose-dependent manner. The relaxation induced by L-Arginine reached 15.6% at 5.10(-4) M vs. 16.5% at AMP 5.10(-4) M under the same experimental conditions. Nitric oxide (NO) synthase inhibitor N-nitro-L-arginine strongly inhibited the relaxing effect provoked by AMP, suggesting that the action mechanism of this nucleotide is related to the NO pathway. The combination of L-Arginine at 5.10(-4) M with AMP at different doses ranging from 5.10(-4) M to 10(-3) M significantly amplified the relaxing response up to 40.7% and 58%, respectively. CONCLUSIONS: Our results demonstrate that AMP induces a relaxing effect on the female rabbit corpora. They also show that L-Arginine and AMP can potentiate each other and that a synergistic effect can be obtained by their combined use. Because only slight differences exist between both sexes in response to NO donors and/or nucleotide purines or in their use together, it is very likely that close biochemical mechanisms, although not to the same degree and not quite similar, are involved in the engorgement of the penis and the clitoris of New Zealand White rabbits. Stücker O, Pons C, Neuzillet Y, Laemmel E, and Lebret T. Original research-sexual medicine: Effects of adenosine monophosphate used in combination with L-Arginine on female rabbit corpus cavernosum tissue. Sex Med 2014;2:1-7.
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CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is caused by mutations in the Notch3 receptor expressed at the surface of vascular smooth muscle cells. The functional consequences of the disease at the peripheral microcirculation level are incompletely elucidated. In this study, we aimed to assess, in vivo, the endothelium-dependent and independent vasodilation of the skin microvasculature in CADASIL patients. Twenty-three affected subjects were compared with 23 gender and age-matched controls. The brachial artery endothelium-dependent and endothelium-independent vasodilation were assessed after forearm cuff occlusion and nitroglycerin administration. Skin vasoreactivity to transcutaneous administration of acetylcholine and sodium nitroprussiate, and after postocclusive hyperemia were measured by Laser Doppler flowmetry. The maximum changes in the diameter of the brachial artery after the cuff release or after nitroglycerin administration did not differ between patients and controls. With iontopheresis, only the peak value of the dose response was found decreased in normocholesterolemic patients after nitroprussiate administration. The postocclusive test revealed a large increase of the time to peak value and whole duration of the hyperemic response in CADASIL patients. The results of this study show that the skin vasoreactivity is altered in CADASIL. Particularly, the kinetics of reactive hyperemia after cuff occlusion is dramatically changed with a lengthened and delayed response. This characteristic pattern may be related to the specific ultrastructural modifications related to Notch3 gene mutations involving smooth muscle cells in the microvasculature.