Millgård J, Lind L
Department of Internal Medicine, University Hospital of Uppsala, Sweden.
J Cardiovasc Pharmacol. 1998 Sep;32(3):406-12. doi: 10.1097/00005344-199809000-00011.
Several studies indicated an abnormal endothelium-dependent vasodilation (EDV) in hypertensive patients, but no study has systematically investigated the effects of different pharmacologic classes of antihypertensive drugs on EDV. This study aimed to evaluate the effects of three different antihypertensive regimens [angiotensin-converting enzyme (ACE) inhibition, calcium channel blockade, and beta-blockade] on EDV when given locally in the forearm at a constant blood pressure. The increase in forearm blood flow (FBF) during local intraarterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation, EIDV) was measured in young, normotensive subjects by venous occlusion plethysmography, before and during concomitant local intraarterial infusion of any of the antihypertensive drugs. Without changing baseline FBF, enalaprilat (n=6, 2.4 mg/h) potentiated the increase in FBF induced by MCh [from 22.6+/-2.3 (SD) to 25.4+/-2.3 ml/min/100 ml tissue at 4 microg/min; p < 0.05], but the response to SNP was unchanged. Local intraarterial verapamil infusion (n=6), at a dose individually titrated to keep baseline FBF unchanged, did not alter the response to MCh infusion, whereas the response to SNP was potentiated. A higher dose of verapamil (n=6), which increased baseline FBF, increased both EDV and EIDV significantly in parallel (p < 0.05). The local propranolol infusion (n=6, 1.2 mg/h) attenuated the FBF response to MCh significantly (from 28.9+/-5.7 to 21.5+/-3.2 ml/min/100 ml tissue at 4 microg/min; p < 0.05), whereas both baseline FBF and the response to SNP were unchanged. In conclusion, this investigation showed that commonly used antihypertensive drugs affect endothelial vasodilator function in a different ways. ACE inhibition enhanced EDV, whereas a nonselective beta-blocker attenuated EDV. The calcium channel blocker, verapamil, improved both EDV and EIDV, probably by a direct effect on the vascular smooth-muscle cells.
多项研究表明高血压患者存在内皮依赖性血管舒张功能异常（EDV），但尚无研究系统地探究不同药理类别的降压药物对EDV的影响。本研究旨在评估三种不同的降压方案[血管紧张素转换酶（ACE）抑制、钙通道阻滞和β受体阻滞]在维持恒定血压的情况下局部应用于前臂时对EDV的影响。通过静脉阻断体积描记法，在年轻的血压正常受试者局部动脉内输注任何一种降压药物之前及期间，测量局部动脉内输注乙酰甲胆碱（MCh；诱导EDV）和硝普钠（SNP；诱导非内皮依赖性血管舒张，EIDV）时前臂血流量（FBF）的增加情况。在不改变基线FBF的情况下，依那普利拉（n = 6，2.4 mg/h）增强了MCh诱导的FBF增加[在4 μg/min时，从22.6±2.3（标准差）增加到25.4±2.3 ml/min/100 ml组织；p < 0.05]，但对SNP的反应未改变。局部动脉内输注维拉帕米（n = 6），剂量根据个体情况调整以保持基线FBF不变，未改变对MCh输注的反应，而对SNP的反应增强。更高剂量的维拉帕米（n = 6）增加了基线FBF，同时显著平行增加了EDV和EIDV（p < 0.05）。局部输注普萘洛尔（n = 6，1.2 mg/h）显著减弱了对MCh的FBF反应（在4 μg/min时，从28.9±5.7降至21.5±3.2 ml/min/100 ml组织；p < 0.05），而基线FBF和对SNP的反应均未改变。总之，本研究表明常用的降压药物以不同方式影响内皮舒张功能。ACE抑制增强了EDV，而非选择性β受体阻滞剂减弱了EDV。钙通道阻滞剂维拉帕米可能通过对血管平滑肌细胞的直接作用改善了EDV和EIDV。
