Chronic treatment with progesterone but not medroxyprogesterone acetate restores the endothelial control of vascular tone in the mesenteric artery of ovariectomized rats
Chronic treatment with progesterone but not medroxyprogesterone acetate restores the endothelial control of vascular tone in the mesenteric artery of ovariectomized rats
复制标题
DOI：
10.1097/01.gme.0000097847.95550.e3
复制
发表时间：
2004-05-01
影响因子：
2.7
通讯作者：
Schini-Kerth, VB
中科院分区：
文献类型：
--
作者：
Chataigneau, T;Zerr, M;Schini-Kerth, VB
目的：为了研究是否长期管理的天然激素孕酮或合成孕激素，醋酸甲羟孕酮，卵巢切除大鼠影响内皮控制的动脉张力在离体肠系膜动脉。设计：假手术大鼠每天接受皮下注射溶剂（芝麻油），而卵巢切除大鼠接受芝麻油，孕酮（22 mg kg（-1）/天）或醋酸甲羟孕酮（22毫克/公斤（-1）/天）4周，根据各自的组。去甲肾上腺素引起的收缩显著增加（约200%，10 μ M）的N-w-硝基-L-精氨酸，一氧化氮合酶抑制剂，在完整的肠系膜动脉环从假手术，但不是从卵巢切除组。黄体酮但不是甲羟孕酮处理恢复了N-硝基-L-精氨酸对苯肾上腺素诱导的收缩的增强作用（在10 μ M时约为180%）。在所有组中，对苯肾上腺素的收缩不受Charybdotoxin加apamin（两种内皮源性超极化因子介导反应的抑制剂）组合的影响。乙酰胆碱引起的内皮依赖性舒张，这是部分抑制的N-硝基-L-精氨酸和N-硝基-L-精氨酸加蛇毒和apamin的组合取消，在所有组中。乙酰胆碱诱导类似的charybdotoxin和apamin敏感的hyperpolarizations在完整的肠系膜动脉节段从所有group.Conclusions：慢性给药的孕酮，但不甲羟孕酮，卵巢切除大鼠恢复的内皮依赖性衰减的收缩反应苯肾上腺素在肠系膜动脉环通过内皮形成一氧化氮。因此，增强内皮细胞对动脉壁的保护作用可能有助于某些含孕激素制剂在激素治疗期间的有益作用。
Objective: To examine whether chronic administration of the natural hormone progesterone or a synthetic progestogen, medroxyprogesterone acetate, to ovariectomized rats affects the endothelial control of arterial tone in the isolated mesenteric artery.Design: Sham-operated rats received a daily subcutaneous injection of solvent (sesame oil), whereas ovariectomized rats received either sesame oil, progesterone (22 mg kg(-1)/day), or medroxyprogesterone acetate (22 mg kg(-1)/day) for 4 weeks, according to their respective group.Results: Pherylephrine-induced contractions were significantly increased (about 200% at 10 muM) by N-w-nitro-L-arginine, a nitric oxide synthase inhibitor, in intact mesenteric arterial rings from the sham-operated but not from the ovariectomized group. The progesterone but not the medroxyprogesterone treatment restored the potentiating effect of N-w-nitro-L-arginine on phenylephrine-induced contraction (about 180% at 10 muM). Contractions to phenylephrine were not affected by the combination of charybdotoxin plus apamin, two inhibitors of endothelium-derived hyperpolarizing factor-mediated responses, in all groups. Acetylcholine induced endothelium-dependent relaxations, which were partially inhibited by Nw-nitro-L-arginine and abolished by the combination of N-w-nitro-L-arginine plus charybdotoxin and apamin, in all groups. Acetylcholine induced similar charybdotoxin and apamin-sensitive hyperpolarizations in intact mesenteric artery segments from all groups.Conclusions: Chronic administration of progesterone, but not medroxyprogesterone, to ovariectomized rats restores the endothelium-dependent attenuation of contractile responses to phenylephrine in mesenteric arterial rings through the endothelial formation of nitric oxide. Thus, an enhancement of the protective effect of endothelial cells on the arterial wall might contribute to the beneficial effect of certain progestogen-containing preparations during hormonal treatment.