Münter K, Hergenröder S, Jochims K, Kirchengast M
Department of Preclinical Cardiology, Knoll AG, Ludwigshafen, Germany.
J Am Soc Nephrol. 1996 May;7(5):681-6. doi: 10.1681/ASN.V75681.
Previous studies have demonstrated differences in the progression to glomerulosclerosis with the use of calcium channel blockers (CCB). The results with angiotensin-converting enzyme (ACE) inhibitors are more consistent. Moreover, only two studies have examined the combined effects of these drug classes on the development of glomerulosclerosis. The aim of the study presented here was to test the hypothesis that nonhypotensive doses of the combination (VT) of a nondihydropyridine CCB, verapamil (V), and an ACE-inhibitor, trandolapril (T), will slow the development of glomerulosclerosis better than either agent alone in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were randomized to treatment in one of three groups with nonhypotensive doses of these agents; a fourth group served as control (C). The control rats developed significant increases in proteinuria compared with the other groups (C, 190 +/- 35 mg.kg-1.d-1 versus VT, 19 +/- 12 mg.kg-1.d-1; P < 0.05). This finding correlated with the degree of glomerulosclerosis (mean severity grading for C, 3.31 +/- 0.21 versus VT, 1.6 +/- 0.51; P < 0.05). Moreover, there was no significant reduction in arterial pressure between these groups (C, 282 +/- 5 versus VT, 259 +/- 13 mm Hg; P = 0.12). Despite persisting hypertension, the rise in proteinuria was also attenuated in both the V group (57 +/- 21 mg.kg-1.d-1) and the T group (43 +/- 24 mg.kg-1.d-1). However, compared with the control rats, kidney morphology was unchanged. Lastly, creatinine clearance was better preserved in the VT group compared with the control group (C, 0.57 +/- 0.01 versus VT, 0.74 +/- 0.06 mL.min-1.100 g-1; P < 0.05). It was concluded that the combination of nonhypotensive doses of VT attenuates the rise in proteinuria and progression to glomerulosclerosis. This study supports the concept that VT may have effects on the glomerulus that are independent of blood pressure reduction.
以往研究已证实，使用钙通道阻滞剂（CCB）时肾小球硬化的进展存在差异。血管紧张素转换酶（ACE）抑制剂的结果更为一致。此外，仅有两项研究考察了这些药物类别对肾小球硬化发展的联合作用。本文所呈现研究的目的是检验这样一个假设：在易发生卒中的自发性高血压大鼠（SHRSP）中，非二氢吡啶类CCB维拉帕米（V）与ACE抑制剂trandolapril（T）的非降压剂量联合用药（VT），在减缓肾小球硬化发展方面比单独使用任何一种药物效果更好。将SHRSP随机分为三组，分别用这些药物的非降压剂量进行治疗；第四组作为对照组（C）。与其他组相比，对照大鼠的蛋白尿显著增加（C组，190±35mg·kg⁻¹·d⁻¹，而VT组为19±12mg·kg⁻¹·d⁻¹；P<0.05）。这一发现与肾小球硬化程度相关（C组平均严重程度评分为3.31±0.21，而VT组为1.6±0.51；P<0.05）。此外，这些组之间的动脉血压没有显著降低（C组，282±5，而VT组为259±13mmHg；P = 0.12）。尽管高血压持续存在，但V组（57±21mg·kg⁻¹·d⁻¹）和T组（43±24mg·kg⁻¹·d⁻¹）的蛋白尿增加也有所减轻。然而，与对照大鼠相比，肾脏形态没有变化。最后，与对照组相比，VT组的肌酐清除率得到了更好的维持（C组，0.57±0.01，而VT组为0.74±0.06mL·min⁻¹·100g⁻¹；P<0.05）。得出的结论是，非降压剂量的VT联合用药可减轻蛋白尿增加及向肾小球硬化的进展。该研究支持这样一种观点，即VT可能对肾小球有独立于血压降低的作用。
