Disparate effects of angiotensin II antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension: potential role of nephrin
Disparate effects of angiotensin II antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension: potential role of nephrin
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DOI：
10.1097/00004872-200301000-00031
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发表时间：
2003-01-01
影响因子：
4.9
通讯作者：
Allen, TJ
中科院分区：
文献类型：
--
作者：
Davis, BJ;Cao, ZM;Allen, TJ
目的和设计探讨各种抗高血压方案的效果，这些方案使用一系列药物，包括血管紧张素II 1型受体拮抗剂缬沙坦，作为单药治疗或与两种亚类钙通道阻滞剂（CCB）联合治疗，可达到相似的血压控制效果。（二氢吡啶，二氢吡啶和苯基烷基胺，维拉帕米）对肾病进展和足细胞狭缝孔蛋白表达的影响，结果缬沙坦治疗可降低收缩压，如通过无线遥测评估的（135 +/- 3 vs糖尿病患者153 +/- 6 mmHg），以及将白蛋白排泄率的增加延迟约50%。缬沙坦与氨氯地平或维拉帕米联合治疗在降低血压方面与缬沙坦单药治疗（缬沙坦+氨氯地平129 +/- 4缬沙坦+维拉帕米133 +/- 6 mmHg;）同样有效，但在降低蛋白尿方面效果不佳。在缬沙坦单药治疗中观察到肾小球硬化的减少，而在缬沙坦+曲马多联合治疗中观察到损伤的减少较少，尽管血压降低相似。减少nephrin，在糖尿病大鼠的衰减缬沙坦单药治疗，但不是由其他treatment.Conclusions本研究的结果表明，尽管类似的降低血压，除了CCB的所有拮抗剂未能提供类似的肾保护观察到的等效方案缬沙坦作为单药治疗。此外，糖尿病动物肾小球nephrin表达的减少仅通过缬沙坦治疗消除，该治疗在该模型中延缓白蛋白尿的发展是最有效的。(C)2003年利平科特威廉姆斯威尔金斯。
Objective and design To explore the effects of various antihypertensive regimes which achieve similar blood pressure control using a range of agents including the angiotensin II type 1 receptor antagonist, valsartan, as monotherapy or in combination with two subclasses of calcium channel blockers (CCBs) (the dihydropyridine, amlodipine and the phenylalkylamine, verapamil) on the progression of renal disease and the expression of the podocyte slit pore protein, nephrin in an accelerated model of diabetic nephropathy.Results Valsartan treatment reduced systolic blood pressure as assessed by radiotelemetry (135 +/- 3 versus diabetic 153 +/- 6 mmHg) as well as retarding the increase in albumin excretion rate by approximately 50%. Combination therapy of valsartan with either amlodipine or verapamil was equally effective in reducing blood pressure to valsartan monotherapy (valsartan + amlodipine 129 +/- 4 valsartan + verapamil 133 +/- 6 mmHg;) but was not as effective at reducing albuminuria. A reduction in glomerulosclerosis was observed with valsartan monotherapy with less reduction in injury with the valsartan + amlodipine combination, despite a similar reduction in blood pressure. The decrease in nephrin, in diabetic rats was attenuated by valsartan monotherapy, but not by other treatments.Conclusions The results of this study demonstrate that despite a similar reduction in blood pressure, the addition of the CCB amlodipine to the All antagonist failed to provide similar renoprotection to that observed with an equihypotensive regimen of valsartan as monotherapy. Furthermore, the depletion in glomerular nephrin expression in diabetic animals was only abrogated by valsartan treatment the therapy which was most effective at retarding the development of albuminuria in this model. (C) 2003 Lippincott Williams Wilkins.