"Pulse" Treatment With High-Dose Angiotensin Blocker Reverses Renal Arteriolar Hypertrophy and Regresses Hypertension
"Pulse" Treatment With High-Dose Angiotensin Blocker Reverses Renal Arteriolar Hypertrophy and Regresses Hypertension
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DOI：
10.1161/hypertensionaha.108.122721
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发表时间：
2009-01-01
期刊：
影响因子：
8.3
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Ishiguro, Kimiko;Hayashi, Kaori;Itoh, Hiroshi
高血压治疗的最终目标之一是使已形成的高血压永久逆转（“消退”）。我们的目的是检查肾素-血管紧张素系统抑制剂的高剂量“脉冲”治疗是否可以引起已形成的高血压的消退，并将这种作用与小动脉肥大的逆转和血管基质金属蛋白酶活性的变化联系起来。首先，对 16 周龄雄性自发性高血压大鼠（n = 60）进行为期 2 周的高剂量血管紧张素转换酶抑制剂（依那普利）、血管紧张素受体阻滞剂（坎地沙坦）、钙通道阻滞剂（硝苯地平）或血管扩张剂（肼屈嗪）脉冲治疗，并限制盐摄入量或不限制盐摄入量，并检查对血压的长期影响。其次，用血管紧张素受体阻滞剂或钙通道阻滞剂治疗自发性高血压大鼠，比较对肾脏基因表达、小动脉结构和血管基质金属蛋白酶的影响。在尾套法的限制范围内，用不同的抗高血压药物治疗自发性高血压大鼠，在脉冲治疗过程中引起明显相似的血压降低。停止用药后，用肾素-血管紧张素系统抑制剂治疗的大鼠血压在 4 个月内仍保持降低 >30 至 40 mm Hg。钙通道阻滞剂或血管扩张剂没有观察到这种作用。两周的血管紧张素受体阻滞剂治疗可显着逆转小动脉肥大，尤其是小肾小动脉（30至100μm），同时基质金属蛋白酶13的表达和活性增加。总之，血管紧张素受体阻滞剂短暂高剂量脉冲治疗引起自发性高血压大鼠血管基质金属蛋白酶活性的变化、肾小动脉肥大的特异性逆转和高血压的消退。 （高血压。2009；53：83-89。）
One ultimate goal of hypertension therapy is to cause permanent reversal ("regression") of already established hypertension. Our aim was to examine whether high-dose "pulse" treatment with a renin-angiotensin system inhibitor could cause regression of established hypertension and to link this action to reversal of arteriolar hypertrophy and changes in vascular matrix metalloproteinase activities. First, 16-week-old male spontaneously hypertensive rats (n = 60) were pulse treated for 2 weeks with high-dose angiotensin-converting enzyme inhibitor (enalapril), angiotensin receptor blocker (candesartan), calcium channel blocker (nifedipine), or vasodilator (hydralazine) with or without salt restriction, and the long-term effects on blood pressure were examined. Second, spontaneously hypertensive rats were treated with angiotensin receptor blocker or calcium channel blocker, and the effects on renal gene expressions, arteriolar structure, and vascular matrix metalloproteinase were compared. Treatment of spontaneously hypertensive rats with different antihypertensive agents caused apparently similar reductions in blood pressure during the course of the pulse treatment, within the limitations of the tail-cuff method. After cessation of medications, blood pressure in the rats treated with renin-angiotensin system inhibitor remained reduced by >30 to 40 mm Hg for 4 months. No such effect was seen with calcium channel blocker or vasodilator. The 2-week angiotensin receptor blocker treatment induced a marked reversal of the arteriolar hypertrophy specifically in the small (30 to 100 mu m) renal arterioles, together with increased expression and activity of matrix metalloproteinase-13. In conclusion, transient high-dose pulse treatment with angiotensin receptor blocker caused changes in vascular matrix metalloproteinase activity, specific reversal of renal arteriolar hypertrophy, and regression of hypertension in spontaneously hypertensive rats. (Hypertension. 2009; 53: 83-89.)