Biological Sciences and Human Health Section, Department of Biological Sciences, Faculty of Higher Studies Cuautitlan, National Autonomous University of México, México.
J Pharmacol Sci. 2013;122(3):184-92. doi: 10.1254/jphs.12248fp. Epub 2013 Jul 2.
The in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP, was induced by a single administration of STZ (55 mg·kg(-1), i.p.). In the drug-treated groups, treatment with bis-1,4-DHP (10 mg·kg(-1)·day(-1)) started one week before diabetes induction; bis-1,4-DHP was dissolved in DMSO (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). Parameters evaluated were body weight, blood glucose, albuminuria, proteinuria, creatinine, urea excretion, kidney's weight / body weight ratio, and kidney perfusion pressure in all rat groups at different times of diabetes (2, 4, 6, and 10 weeks). Kidney weight of diabetic rats significantly increased vs. control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats at different times of diabetes. The ratios % kidney weight / 100 g body weight were different between control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats vs. diabetic rats (P < 0.05). Kidney perfusion pressure was decreased by diabetes, while it was partially recovered by bis-1,4-DHP treatment in response to phenylephrine. Bis-1,4-DHP had a tendency to decrease hyperglycemia vs. diabetic rats, even though glycemia was too high as compared with controls, and it ameliorated albuminuria, creatinine, and urea excretion, suggesting a favorable effect on renal haemodynamics. Bis-1,4-DHP, by inhibiting Ca(2+) entrance, induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction, but does not have significant impact on hyperglycemia.
体内有效性 4-二氢吡啶（双-1,4-DHP），一种新的钙通道阻滞剂，作为一种肾保护剂在分离灌注肾中通过确定其对糖尿病大鼠肾损伤相关参数的影响来评估。雄性 Wistar 大鼠的糖尿病，对照组，糖尿病，对照组+双-1,4-DHP，和糖尿病+双-1,4-DHP，通过单次 STZ（55mg·kg(-1)，ip）给药诱导。在药物治疗组中，在糖尿病诱导前一周开始用双-1,4-DHP（10mg·kg(-1)·天(-1)）治疗；双-1,4-DHP 溶解在 DMSO（0.3%）中，并悬浮在羧甲基纤维素（3%）的饮用水中。在糖尿病的不同时间（2、4、6 和 10 周）评估所有大鼠组的体重、血糖、白蛋白尿、蛋白尿、肌酐、尿素排泄、肾重/体重比和肾灌注压。糖尿病大鼠的肾重与对照组、对照组+双-1,4-DHP 和糖尿病+双-1,4-DHP 大鼠相比，在不同时间均显著增加。对照组、对照组+双-1,4-DHP 和糖尿病+双-1,4-DHP 大鼠的肾重/100g 体重的比例与糖尿病大鼠不同（P <0.05）。肾灌注压因糖尿病而降低，而双-1,4-DHP 治疗部分恢复对苯肾上腺素的反应。双-1,4-DHP 有降低高血糖的趋势与糖尿病大鼠相比，即使血糖与对照组相比过高，并且改善白蛋白尿、肌酐和尿素排泄，表明对肾功能有有利影响。双-1,4-DHP 通过抑制 Ca(2+)进入，诱导肾血管床扩张，从而可能对糖尿病引起的肾功能障碍具有肾保护作用，但对高血糖无显著影响。
