Mabe K, Ito M, Okamura H
Department of Obstetrics and Gynecology, Kumamoto University Medical School, Japan.
Obstet Gynecol. 1992 Aug;80(2):291-5.
We examined the effects of norethisterone and/or mestranol on the pressor response to angiotensin II in 20 healthy men.
Four study protocols were used: I) mestranol 0.08 mg/day for 6 days followed by mestranol plus norethisterone 20 mg/day for 6 days, II) mestranol 0.16 mg/day for 6 days followed by norethisterone alone 10 mg/day for 6 days, III) mestranol 0.24 mg/day followed by norethisterone 20 mg/day for 6 days, and IV) norethisterone 20 mg/day for 6 days. The angiotensin II dose to elicit a 20-mmHg rise in diastolic blood pressure was considered the effective pressor dose. This was determined before each protocol, at the end of the mestranol-alone portion, and at the end of the norethisterone portion. Subjects in study III also underwent measurement of plasma prostanoid levels, plasma renin activity and concentration, and estradiol and progesterone just before each angiotensin II infusion. Subjects in studies I and III underwent measurement of mean platelet volume, complete blood counts, liver function tests, and coagulation factors before each angiotensin II infusion.
Whereas mestranol had no apparent effect on angiotensin II pressor response, norethisterone at a dose of 20 mg/day (with or without concurrent mestranol administration) caused a significant decrease in pressor responsiveness to angiotensin II. No changes in plasma prostanoids or renin could be found that would account for the change in pressor response.
These findings indicate that the refractoriness to angiotensin II induced by norethisterone was related to its progestogenic properties.
我们研究了炔诺酮和/或炔雌醇甲醚对20名健康男性血管紧张素II升压反应的影响。
采用了四种研究方案：I）炔雌醇甲醚0.08毫克/天，持续6天，随后炔雌醇甲醚加炔诺酮20毫克/天，持续6天；II）炔雌醇甲醚0.16毫克/天，持续6天，随后单独使用炔诺酮10毫克/天，持续6天；III）炔雌醇甲醚0.24毫克/天，随后炔诺酮20毫克/天，持续6天；IV）炔诺酮20毫克/天，持续6天。引起舒张压升高20毫米汞柱的血管紧张素II剂量被视为有效升压剂量。这在每个方案之前、仅使用炔雌醇甲醚部分结束时以及炔诺酮部分结束时确定。研究III中的受试者在每次输注血管紧张素II之前还进行了血浆类前列腺素水平、血浆肾素活性和浓度以及雌二醇和孕酮的测量。研究I和III中的受试者在每次输注血管紧张素II之前进行了平均血小板体积、全血细胞计数、肝功能测试和凝血因子的测量。
虽然炔雌醇甲醚对血管紧张素II升压反应没有明显影响，但20毫克/天的炔诺酮（无论是否同时给予炔雌醇甲醚）导致对血管紧张素II的升压反应性显著降低。未发现血浆类前列腺素或肾素的变化可以解释升压反应的变化。
这些发现表明，炔诺酮诱导的对血管紧张素II的耐受性与其孕激素特性有关。
