Rizzoni D, Castellano M, Porteri E, Bettoni G, Muiesan M L, Cinelli A, Zulli R, Rosei E A
Cattedra di Semeiotica e Metodologia Medica, U.O.P. Scienze Mediche, University of Brescia, Italy.
Am J Hypertens. 1997 Sep;10(9 Pt 1):1034-43. doi: 10.1016/s0895-7061(97)00166-0.
The aim of this study was to evaluate the delayed effects of an angiotensin converting enzyme (ACE) inhibitor on blood pressure and on structural and functional alterations in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). The ACE inhibitor fosinopril (25 mg/kg/day) was administered according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a second group from 8 to 12 weeks of age (n = 15), and in a third group from 4 to 12 weeks of age (n = 12). Eighteen untreated SHR and 18 untreated Wistar-Kyoto rats served as controls. About half the animals in each group were killed at 13 weeks of age, and the remaining were killed at 38 weeks of age. After death, relative left ventricular mass (left ventricular weight/body weight) was calculated. Vascular morphology (media:lumen ratio) and function (responses to norepinephrine and acetylcholine) in mesenteric small resistance arteries were then assessed using a micromyographic technique. Short-term fosinopril, given either before or after the development of hypertension, persistently reduced (but did not normalize) systolic blood pressure, vascular structural alterations, and reactivity to norepinephrine in mesenteric resistance arteries in SHR. These favorable effects were maintained at least for 26 to 30 weeks after treatment withdrawal. The endothelium-dependent vasodilator response to acetylcholine was improved at 13 but not at 38 weeks of age, in treated SHR. Therefore, the vascular response to norepinephrine seems to be dependent mainly on the structure of the vessels, whereas endothelial function is probably more linked to the hemodynamic load.
本研究的目的是评估血管紧张素转换酶（ACE）抑制剂对自发性高血压大鼠（SHR）血压以及肠系膜小阻力动脉结构和功能改变的延迟作用。ACE抑制剂福辛普利（25毫克/千克/天）按照三种不同的给药方案给药：一组SHR从4周龄至8周龄给药（n = 12），第二组从8周龄至12周龄给药（n = 15），第三组从4周龄至12周龄给药（n = 12）。18只未治疗的SHR和18只未治疗的Wistar - Kyoto大鼠作为对照。每组约一半的动物在13周龄时处死，其余的在38周龄时处死。处死动物后，计算相对左心室质量（左心室重量/体重）。然后使用微血管描记技术评估肠系膜小阻力动脉的血管形态（中膜：管腔比值）和功能（对去甲肾上腺素和乙酰胆碱的反应）。短期给予福辛普利，无论在高血压发生之前还是之后给药，均可持续降低（但未使其正常化）SHR肠系膜阻力动脉的收缩压、血管结构改变以及对去甲肾上腺素的反应性。这些有益作用在停药后至少维持26至30周。在接受治疗的SHR中，13周龄时对乙酰胆碱的内皮依赖性血管舒张反应有所改善，但38周龄时未改善。因此，血管对去甲肾上腺素的反应似乎主要取决于血管结构，而内皮功能可能与血流动力学负荷的关系更为密切。
