Millgård J, Hägg A, Sarabi M, Lind L
Department of Internal Medicine, University Hospital of Uppsala, Sweden.
J Hum Hypertens. 1998 Aug;12(8):511-6. doi: 10.1038/sj.jhh.1000665.
The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium-nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study. First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P < 0.001 at MCh 4 microg/min). Second, although the two drugs induced a similar decline in blood pressure (BP) 1 h after administration (-11 to 10 mm Hg/-8 to 7 mm Hg), captopril significantly potentiated the vasodilator response to MCh (+32+/-13%, MCh 4 micr og/min, P < 0.01) but not SNP, while nifedipine did not significantly alter the response to either MCh or SNP. The improvement in vasodilator response to MCh induced by captopril was closely related to the reduction in BP (r = 0.72, P < 0.01). Third, in the pilot study, 3 months of captopril treatment induced a significant potentiation of the vasodilator response to MCh (+34+/-17%, MCh 4 microg/min, P < 0.05) in parallel with a significant BP reduction (-22+/-24/13+/-13 mm Hg, P < 0.05), while the response to SNP was unchanged. In conclusion, the present study confirmed that essential hypertension is associated with a defect in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients shortly after administration of captopril, but not nifedipine. In addition, a significant beneficial effect on EDV was seen in a small pilot study during long-term treatment with captopril.
本研究旨在探讨血管紧张素转换酶（ACE）抑制剂卡托普利和钙拮抗剂硝苯地平对高血压患者前臂内皮依赖性血管舒张（EDV）的影响。23名未经治疗的中年高血压患者，通过局部动脉内输注乙酰甲胆碱（MCh，评估EDV）和硝普钠（SNP，评估非内皮依赖性血管舒张，EIDV），在随机、双盲服用卡托普利（25mg）或硝苯地平（10mg）之前及之后1小时，对其前臂的EDV和非内皮依赖性血管舒张进行评估。一个匹配的血压正常对照组仅在基线条件下进行研究。在一项开放的初步研究中，对5名高血压患者在每日两次服用25mg卡托普利治疗3个月后也进行了评估。首先，与血压正常的对照组相比，高血压患者中由乙酰甲胆碱（MCh）而非硝普钠诱导的血管舒张明显减弱（MCh 4μg/min时P<0.001）。其次，尽管两种药物在给药1小时后引起了相似的血压（BP）下降（-11至10mmHg / -8至7mmHg），但卡托普利显著增强了对MCh的血管舒张反应（+32±13%，MCh 4μg/min，P<0.01），但对硝普钠无此作用，而硝苯地平对MCh或硝普钠的反应均无显著改变。卡托普利诱导的对MCh血管舒张反应的改善与血压降低密切相关（r = 0.72，P<0.01）。第三，在初步研究中，3个月的卡托普利治疗在使血压显著降低（-22±24/13±13mmHg，P<0.05）的同时，诱导了对MCh血管舒张反应的显著增强（+34±17%，MCh 4μg/min，P<0.05），而对硝普钠的反应未改变。总之，本研究证实原发性高血压与EDV缺陷有关。此外，高血压患者在服用卡托普利后不久可见EDV改善，但服用硝苯地平后未见改善。另外，在一项关于卡托普利长期治疗的小型初步研究中，观察到对EDV有显著的有益作用。
