Lee R M, Lu M, Gillies L, Werstiuk E S
Department of Anaesthesia, Faculty of Health Sciences, McMaster University, Hamilton, Ontario.
Can J Cardiol. 1997 Sep;13(9):831-5.
To determine the effect of perindopril treatment and treatment withdrawal in the prevention of hypertension in adult male spontaneously hypertensive rats (SHR).
Beginning at 15 weeks of age, male SHR were treated with either distilled water (control) or different daily dosages of perindopril (1, 2 or 4 mg/kg) by gavage for 10 weeks, followed by 10 weeks of treatment withdrawal. Systolic blood pressure, heart rate and body weight of adult SHR were determined at regular intervals before, during and after the treatment withdrawal periods. At the end of the treatment withdrawal period, plasma and tissue samples were taken for measurement of noradrenaline levels. Angiotensin-converting enzyme (ACE) activity in the plasma from adult SHR and Wistar-kyoto (WKY) rats treated with perindopril 4 mg/kg for two weeks was measured by a radioassay method 6 and 24 h after treatment.
Treatment with perindopril caused a dose-dependent lowering of blood pressure in SHR during the 10-week treatment. After withdrawal of the treatment, persistent lowering of blood pressure was found in SHR treated with higher dosages (2 or 4 mg/kg), but not in the 1 mg/kg group. There was no difference in the tissue level of noradrenaline among the control group and SHR previously treated with perindopril. In SHR and WKY treated with perindopril for two weeks, plasma level of ACE activity was reduced longer than 24 h compared with their respective controls.
Chronic treatment of adult SHR with perindopril has a dose-dependent effect on the blood pressure of these animals both during and after withdrawal of treatment, but such a treatment had no long term effects on the noradrenaline levels in various tissues.
确定培哚普利治疗及停药对成年雄性自发性高血压大鼠（SHR）高血压预防的影响。
15周龄雄性SHR开始，分别用蒸馏水（对照组）或不同日剂量的培哚普利（1、2或4mg/kg）灌胃10周，随后停药10周。在停药期之前、期间和之后定期测定成年SHR的收缩压、心率和体重。在停药期结束时，采集血浆和组织样本以测量去甲肾上腺素水平。用放射分析法在接受4mg/kg培哚普利治疗两周的成年SHR和Wistar-kyoto（WKY）大鼠治疗后6小时和24小时测量血浆中的血管紧张素转换酶（ACE）活性。
在10周治疗期间，培哚普利治疗使SHR血压呈剂量依赖性降低。停药后，高剂量（2或4mg/kg）治疗的SHR血压持续降低，但1mg/kg组未出现此情况。对照组与先前接受培哚普利治疗的SHR之间，去甲肾上腺素的组织水平无差异。在接受培哚普利治疗两周的SHR和WKY中，与各自对照组相比，血浆ACE活性水平降低超过24小时。
成年SHR长期用培哚普利治疗，在治疗期间和停药后对这些动物的血压有剂量依赖性影响，但这种治疗对各组织中的去甲肾上腺素水平无长期影响。
