Van Bortel L M, Spek J J, Balkestein E J, Sardina M, Struijker Boudier H A
Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
J Hypertens. 1999 May;17(5):701-5. doi: 10.1097/00004872-199917050-00015.
Patients with high pulse pressures have an increased risk for cardiovascular events. Drugs that selectively decrease high pulse pressure may be of interest for these patients. Such drugs have a more pronounced effect on large arteries than on resistance vessels.
To compare the selectivity to large arteries of the new nitric oxide donor sinitrodil with the classic nitrate isosorbide dinitrate in healthy young men in order to investigate whether it is possible to develop drugs that act more selectively on large arteries.
The study had a double-blind, 5-way cross-over design. In randomized order, subjects received a single oral dose of 10 mg sinitrodil, 20 mg sinitrodil, 40 mg sinitrodil, isosorbide dinitrate and placebo. Measurements were performed before and 45 min after administration of the drugs. Between each drug administration, at least 3 days of wash-out was allowed.
The effects of the drugs on large arteries and resistance vessels were assessed by their effects on brachial artery compliance and total peripheral resistance, respectively.
Brachial artery compliance increased gradually with increasing doses of sinitrodil (by 10, 20 and 27% with 10, 20 and 40 mg sinitrodil, respectively). Total peripheral resistance index decreased with isosorbide dinitrate (by 11%) and 40 mg sinitrodil (by 7%), while it remained unchanged with 10 mg and 20 mg sinitrodil.
The results of this study show that it may be possible to develop drugs with a higher selectivity for large arteries. Such drugs may be good candidates to decrease high pulse pressure without substantially decreasing mean and diastolic blood pressures.
脉压高的患者发生心血管事件的风险增加。对于这些患者，选择性降低高脉压的药物可能会引起关注。此类药物对大动脉的作用比对阻力血管的作用更为显著。
比较新型一氧化氮供体西尼地平与经典硝酸盐异山梨醇二硝酸酯对健康年轻男性大动脉的选择性，以研究是否有可能开发出对大动脉具有更高选择性作用的药物。
该研究采用双盲、五路交叉设计。受试者按随机顺序单次口服10毫克西尼地平、20毫克西尼地平、40毫克西尼地平、异山梨醇二硝酸酯和安慰剂。在给药前和给药后45分钟进行测量。每次给药之间至少允许3天的洗脱期。
分别通过药物对肱动脉顺应性和总外周阻力的影响来评估其对大动脉和阻力血管的作用。
随着西尼地平剂量的增加，肱动脉顺应性逐渐增加（10毫克、20毫克和40毫克西尼地平分别使顺应性增加10%、20%和27%）。异山梨醇二硝酸酯（使总外周阻力指数降低11%）和40毫克西尼地平（使总外周阻力指数降低7%）可使总外周阻力指数降低，而10毫克和20毫克西尼地平则使其保持不变。
本研究结果表明，有可能开发出对大动脉具有更高选择性的药物。此类药物可能是降低高脉压而又不显著降低平均血压和舒张压的良好候选药物。
