Response to angiotensin inhibition in rats with sustained renovascular hypertension correlates with response to removing renal artery stenosis.
Response to angiotensin inhibition in rats with sustained renovascular hypertension correlates with response to removing renal artery stenosis.
复制标题
持续肾血管性高血压大鼠对血管紧张素抑制的反应与去除肾动脉狭窄的反应相关。
DOI：
10.1016/s0741-5214(98)70212-5
复制
发表时间：
1998
影响因子：
4.3
通讯作者：
Beierwaltes,WH
中科院分区：
文献类型：
--
作者：
Pipinos,II;Nypaver,TJ;Moshin,SK;Careterro,OA;Beierwaltes,WH
目的持续性（晚期）肾血管性高血压与血浆肾素活性低于早期相关。目前尚不清楚血浆肾素活性的降低在多大程度上反映了肾素-血管紧张素系统影响的减弱。目前还不清楚疾病特征的这种变化是否会影响手术切除肾动脉狭窄以逆转高血压的效果。使用持续（肾动脉夹闭后≥10周）双肾、单夹肾血管性高血压的动物模型，我们假设氯沙坦选择性血管紧张素 II 受体阻断的降压反应强度将反映肾素-血管紧张素系统对高血压的影响，并使我们能够预测对随后手术切除夹子的降压反应。方法 20只体重为 150 只的雄性 Sprague-Dawley 大鼠的左肾动脉至 200 gm 的重量均配有银夹（内径 0.23 mm）。通过尾套体积描记法测量收缩压，持续 10 周。然后给大鼠口服氯沙坦（每天30毫克/公斤）1周，同时监测血压。再过一周恢复后，13 只老鼠接受了手术脱毛，7 只老鼠接受了假修复。最后一周再次监测血压。结果所有两肾单夹大鼠在夹夹10周后均出现高血压（平均收缩压206±10mmHg）。氯沙坦使收缩压降低 36 ± 6 mm Hg。反应各不相同，范围为 3 至 66 毫米汞柱，总体血压未正常化 (170 ± 8 毫米汞柱)。随后的手术松解使收缩压降低了 46 ± 9 mm Hg。尽管总体血压没有正常化（164 ± 7 mm Hg），但反应也是可变的，范围从 10 到 99 mm Hg。松开夹子后血压下降与服用氯沙坦后血压下降高度相关（r = 0.861，p < 0.001）。静息血浆肾素活性（干预前）为每毫升每小时 16 ± 4 ng 血管紧张素 I，不能预测对氯沙坦或手术剪除的反应。接受假手术的大鼠的血压没有统计学上显着的变化。组织学评估显示，去除夹子后，肾动脉未见明显狭窄或内膜增生。结论在持续的双肾单夹肾血管性高血压中，对血管紧张素 II 受体阻断的降压反应减弱，表明晚期高血压变得越来越不依赖于血管紧张素 II。在我们的模型中，持续性肾血管性高血压对 7 天血管紧张素 II 阻断无效的程度高度预测肾动脉狭窄手术修复的最终结果。 （瓦斯克外科杂志 1998 年；28：167-77。）
PurposeSustained (late-phase) renovascular hypertension is associated with lower plasma renin activity than is the early phase. It is not clear to what extent this reduced plasma renin activity reflects diminished influence of the renin-angiotensin system. It also is not clear whether this change in the character of the disease influences the effectiveness of surgical removal of the renal artery stenosis in reversing hypertension. Using an animal model of sustained (≥10 weeks after renal artery clipping) two-kidney, one-clip renovascular hypertension, we hypothesized that the magnitude of the depressor response to selective angiotensin II receptor blockade with losartan would reflect the influence of the renin-angiotensin system on hypertension and enable us to predict the depressor response to subsequent surgical removal of the clip.MethodsThe left renal arteries of 20 male Sprague-Dawley rats weighing 150 to 200 gm were fitted with a silver clip (0.23 mm internal diameter). Systolic blood pressure was measured by means of tail-cuff plethysmography for 10 weeks. Rats were then given losartan orally (30 mg/kg a day) for 1 week while blood pressure was monitored. After an additional week to allow recovery, 13 rats underwent surgical unclipping, and seven underwent sham repair. Blood pressure again was monitored over the final week.ResultsAll two-kidney one-clip rats had hypertension 10 weeks after clipping (mean systolic blood pressure 206 ± 10 mm Hg). Losartan decreased systolic blood pressure by 36 ± 6 mm Hg. The response was variable, ranging from 3 to 66 mm Hg, and overall blood pressure did not normalize (170 ± 8 mm Hg). Subsequent surgical unclipping decreased systolic blood pressure by 46 ± 9 mm Hg. Again the response was variable, ranging from 10 to 99 mm Hg, although overall blood pressure did not normalize (164 ± 7 mm Hg). The decrease in blood pressure after unclipping showed a high correlation with the blood pressure decrease after losartan administration (r = 0.861, p < 0.001). Resting plasma renin activity (before intervention) was 16 ± 4 ng angiotensin I per milliliter per hour and was not predictive of the response to either losartan or surgical unclipping. The rats subjected to sham operations had no statistically significant changes in blood pressure. Histologic evaluation showed patent renal arteries without appreciable stenosis or intimal hyperplasia after removal of the clips.ConclusionsIn sustained two-kidney, one-clip renovascular hypertension, the depressor response to angiotensin II receptor blockade is attenuated, suggesting that late-phase hypertension becomes increasingly angiotensin II-independent. In our model, the extent to which sustained renovascular hypertension becomes refractory to 7 days of angiotensin II blockade is highly predictive of the ultimate outcome of surgical repair of renal artery stenosis. (J Vasc Surg 1998;28:167-77.)