Lee R M, Berecek K H, Tsoporis J, McKenzie R, Triggle C R
Department of Anaesthesia, McMaster University, Hamilton, Ontario, Canada.
Hypertension. 1991 Feb;17(2):141-50. doi: 10.1161/01.hyp.17.2.141.
Treatment of female spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats with captopril was carried out by the addition of the drug in the drinking water throughout pregnancy and lactation and after weaning. At 28 weeks of age, average systolic blood pressure of treated SHR was 113 +/- 3 mm Hg, which was below that of control SHR (188 +/- 3 mm Hg) and WKY rats (124 +/- 3 mm Hg). Body weight and heart rate of the SHR were not affected by the treatment. Tissue level of catecholamines was increased by captopril treatment in the superior cervical ganglia but remained unchanged in the plasma, heart, mesenteric arteries, and the adrenal glands of both SHR and WKY rats. Left ventricular weight, wall thickness, and internal diameter of the left ventricle in the SHR were reduced by the treatment. Morphometric measurements of the mesenteric arteries showed that vascular alterations present in the control SHR were prevented by the treatment. In the superior mesenteric artery and large mesenteric artery, smaller lumen size at maximal relaxation found in the control SHR was normalized to the level of the WKY rats. Hypertrophy of the medial wall in the superior mesenteric, large and small mesenteric arteries, and an increase in the number of smooth muscle cell layers in the large mesenteric artery of the SHR were prevented by the treatment. Perfusion study of the mesenteric vascular bed showed that reactivity of these vessels to norepinephrine was reduced, and sensitivity to norepinephrine (as determined by the effective dose that causes 50% of maximal response) was increased in the SHR by captopril treatment. Sensitivity of the tail artery in response to norepinephrine was not altered by the treatment. We conclude that long-term treatment with captopril of SHR before and after birth prevented the development of hypertension, structural and functional alterations of the mesenteric arteries, and cardiac hypertrophy.
在整个妊娠、哺乳期及断奶后，通过在饮用水中添加卡托普利对雌性自发性高血压大鼠（SHR）和对照Wistar-Kyoto（WKY）大鼠进行治疗。在28周龄时，经治疗的SHR的平均收缩压为113±3 mmHg，低于对照SHR（188±3 mmHg）和WKY大鼠（124±3 mmHg）。卡托普利治疗对SHR的体重和心率没有影响。卡托普利治疗使SHR和WKY大鼠颈上神经节中的儿茶酚胺组织水平升高，但血浆、心脏、肠系膜动脉和肾上腺中的儿茶酚胺水平保持不变。卡托普利治疗使SHR的左心室重量、室壁厚度和左心室内径减小。肠系膜动脉的形态测量显示，该治疗可预防对照SHR中存在的血管改变。在肠系膜上动脉和肠系膜大动脉中，对照SHR在最大舒张时较小的管腔尺寸恢复到WKY大鼠的水平。该治疗可预防SHR肠系膜上动脉、肠系膜大动脉和小动脉中膜壁增厚以及肠系膜大动脉中平滑肌细胞层数增加。肠系膜血管床灌注研究表明，卡托普利治疗可降低SHR中这些血管对去甲肾上腺素的反应性，并增加其对去甲肾上腺素的敏感性（由引起最大反应50%的有效剂量确定）。该治疗未改变尾动脉对去甲肾上腺素的敏感性。我们得出结论，在出生前后对SHR长期使用卡托普利可预防高血压的发展、肠系膜动脉的结构和功能改变以及心脏肥大。
