Luque M, Martin P, Martell N, Fernandez C, Brosnihan K B, Ferrario C M
Hypertension Unit, San Carlos University Hospital, Madrid, Spain.
J Hypertens. 1996 Jun;14(6):799-805. doi: 10.1097/00004872-199606000-00017.
To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7)] and prostaglandins to the acute and long-term antihypertensive actions of captopril in mild-to-moderate essential hypertensive patients.
Blood pressure, cardiac rate and the plasma concentrations of angiotensin I (Ang I), angiotensin II (Ang II), Ang-(1-7), prostaglandin E2 and 6-keto prostaglandin F1 alpha (the breakdown product of prostacyclin) were determined in the peripheral venous blood of 24 essential hypertensive subjects before and 3 h after administration of 50 mg captopril. Eleven of 24 patients completed a 6-month treatment period with captopril monotherapy (50 mg twice a day). The hemodynamic and hormonal response produced by a last 50 mg dose of captopril was determined once again in the 11 subjects who maintained blood pressure control with captopril monotherapy for 6 months.
The fall in blood pressure produced 3 h after drug intake was comparable for the first and the last 50 mg captopril dose. Although the first response to captopril increased plasma levels of Ang I only, the response to the last dose of the drug (6 months after) caused significantly higher levels of Ang I and Ang-(1-7). Neither acute nor chronic therapy with captopril had a significant effect on plasma concentrations of Ang II. Although plasma levels of prostaglandin E2 and 6-keto prostaglandin F1 alpha were not modified by a first exposure to captopril, the concentrations of 6-keto prostaglandin F1 alpha but not prostaglandin E2 rose significantly in subjects treated with the inhibitor for 6 months. A negative correlation was also demonstrated between diastolic blood pressure and plasma Ang-(1-7) levels in the 11 essential hypertensive subjects in whom blood pressure was controlled with captopril monotherapy.
Inhibition of angiotensin converting enzyme with captopril had a significant effect on blood pressure that was not directly accounted for by a suppression of plasma Ang II levels. Continuous therapy with captopril unmasked a contribution of Ang-(1-7) and prostacyclin to the antihypertensive actions of this drug.
评估血管紧张素 -（1 - 7）[Ang -（1 - 7）]和前列腺素在卡托普利对轻至中度原发性高血压患者的急性和长期降压作用中的贡献。
在24例原发性高血压患者服用50 mg卡托普利前及服药后3小时，测定其外周静脉血中的血压、心率以及血管紧张素I（Ang I）、血管紧张素II（Ang II）、Ang -（1 - 7）、前列腺素E2和6 - 酮前列腺素F1α（前列环素的分解产物）的血浆浓度。24例患者中有11例完成了为期6个月的卡托普利单药治疗（50 mg，每日两次）。在11例通过卡托普利单药治疗维持血压控制达6个月的受试者中，再次测定最后一次50 mg剂量卡托普利产生的血流动力学和激素反应。
服药后3小时，首次和最后一次50 mg卡托普利剂量引起的血压下降相当。虽然卡托普利的首次反应仅使Ang I的血浆水平升高，但对最后一剂药物（6个月后）的反应导致Ang I和Ang -（1 - 7）的水平显著升高。卡托普利的急性和慢性治疗对Ang II的血浆浓度均无显著影响。虽然首次接触卡托普利未改变前列腺素E2和6 - 酮前列腺素F1α的血浆水平，但在接受该抑制剂治疗6个月的受试者中，6 - 酮前列腺素F1α的浓度显著升高，而前列腺素E2未升高。在11例通过卡托普利单药治疗控制血压的原发性高血压受试者中，舒张压与血浆Ang -（1 - 7）水平之间也显示出负相关。
卡托普利抑制血管紧张素转换酶对血压有显著影响，这并非直接通过抑制血浆Ang II水平来解释。卡托普利的持续治疗揭示了Ang -（1 - 7）和前列环素在该药物降压作用中的贡献。
