BRIEF ANGIOTENSIN CONVERTING-ENZYME-INHIBITOR TREATMENT IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS REDUCES BLOOD-PRESSURE LONG-TERM
BRIEF ANGIOTENSIN CONVERTING-ENZYME-INHIBITOR TREATMENT IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS REDUCES BLOOD-PRESSURE LONG-TERM
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DOI：
10.1161/01.hyp.16.6.603
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发表时间：
1990-12-01
期刊：
影响因子：
8.3
通讯作者：
LEVER, AF
中科院分区：
文献类型：
--
作者：
HARRAP, SB;VANDERMERWE, WM;LEVER, AF
我们的研究探讨了血管紧张素转换酶（ACE）抑制剂短期治疗后的长期心血管效应在年轻的自发性高血压大鼠（SHR）。在2至6、6至10或2至10周龄时，通过灌胃给予SHR培哚普利（3 mg/kg/天）。每周在尾部测量收缩压，直到25周龄。相应的对照组在相同的时间段内接受蒸馏水。在每个治疗组中，血压在治疗期间显著降低，在治疗停止时升高，但此后稳定在显著低于对照SHR的水平。25周龄时血压的这种差异是由于微球法测定的总外周阻力降低，但血浆肾素活性和血管紧张素II浓度没有差异。在治疗的SHR中，心脏肥大也减少。在一项单独的实验中，6 - 10周龄的培哚普利治疗导致32周龄时肠系膜阻力血管的中膜/管腔比显著降低。6 - 10周龄时，血管紧张素II与培哚普利联合给药不仅可预防培哚普利单独给药对血压的长期影响，而且与未治疗对照SHR的心血管肥大相关。最后，培哚普利给药时间较短（6 - 7周）或在生命后期（20 - 24周）对血压没有显著的长期影响。这些结果表明，在年轻SHR中进行为期4周的ACE抑制剂治疗足以防止遗传性高血压和心血管肥大的充分表达，并且血管紧张素II可能在该模型中高血压的发展中起重要作用，其在以后的生活中的作用不太重要。
Our study examines the long-term cardiovascular effects after a brief period of angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3 mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of age. Systolic blood pressure was measured in the tail weekly until 25 weeks of age. Corresponding control groups received distilled water for the same periods. In each treatment group blood pressure was reduced significantly during treatment, rose when treatment stopped, but plateaued significantly below control SHR thereafter. This difference in blood pressure at 25 weeks of age was due to reduced total peripheral resistance as determined by microsphere methods, but plasma renin activity and angiotensin II concentrations were not different. Cardiac hypertrophy was also reduced in treated SHR. In a separate experiment, perindopril treatment from 6 to 10 weeks of age resulted in a significant reduction in the media/lumen ratios of mesenteric resistance vessels at 32 weeks of age. Concomitant administration of angiotensin II with perindopril from 6 to 10 weeks of age not only prevented the long-term effects on blood pressure seen with perindopril treatment alone but was associated with cardiovascular hypertrophy in excess of untreated control SHR. Finally, perindopril given for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had no significant long-term effects on blood pressure. These results demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is sufficient to prevent the full expression of genetic hypertension and cardiovascular hypertrophy and that angiotensin II might be important in the development of hypertension in this model, its role in later life being less important.