Emonnot Léa, Cohen Richard, Lo Ming
Centre National de la Recherche Scientifique FRE 3075, Interactions Neurovasculaires, Université de Lyon 1, Université de Lyon, Lyon, France.
Am J Hypertens. 2008 Jun;21(6):657-62. doi: 10.1038/ajh.2008.155. Epub 2008 Apr 3.
In Lyon genetically hypertensive (LH) rats with diabetes, the effects of angiotensin converting enzyme (ACE) inhibition with perindopril on the prevention of dyslipidemia and proteinuria were evaluated by comparison with a nonspecific antihypertensive treatment.
Diabetes was induced in 2-day-old male LH rats by intraperitoneal injection of streptozotocin (75 mg/kg). Glucose tolerance (glucose 2 g/kg by gavage), blood pressure (BP), plasma lipids, and urinary protein excretion were studied in: (i) untreated diabetic LH rats, (ii) diabetic LH rats treated from 8 to 16 weeks of age with oral perindopril at a low dose (0.01 mg/kg/day), (iii) similar rats treated with oral perindopril for the same duration at a high dose (1 mg/kg/day), and (iv) similar rats treated for the same duration with a triple therapy regimen consisting of hydralazine, hydrochlorothiazide, and reserpine (75, 15, and 0.75 mg/kg/day, respectively).
The neonatal administration of streptozotocin in LH rats increased nonfasting glycemia and induced a marked glucose intolerance which was accompanied by further increases in BP, plasma cholesterol, and urinary protein excretion. None of the treatments was able to modify glucose tolerance in diabetic LH rats. The low dose of perindopril was ineffective in the prevention of hypertension, dyslipidemia, and proteinuria in diabetic LH rats, while the high dose of perindopril normalized the BP, reduced the plasma lipids, and lowered the proteinuria. However, in spite of significant reduction in BP, the triple therapy failed to improve dyslipidemia and proteinuria; on the contrary, the therapy worsened these two conditions.
In diabetic LH rats, only ACE inhibition is of benefit to the kidney and lipidemia, thereby demonstrating that antihypertensive regimens may differ in their capacity to protect the target organs and lipid metabolism in a diabetic setting.
在患有糖尿病的里昂遗传性高血压（LH）大鼠中，通过与非特异性抗高血压治疗进行比较，评估培哚普利抑制血管紧张素转换酶（ACE）对预防血脂异常和蛋白尿的作用。
通过腹腔注射链脲佐菌素（75mg/kg）在2日龄雄性LH大鼠中诱导糖尿病。在以下大鼠中研究葡萄糖耐量（通过灌胃给予2g/kg葡萄糖）、血压（BP）、血浆脂质和尿蛋白排泄：（i）未经治疗的糖尿病LH大鼠，（ii）8至16周龄口服低剂量（0.01mg/kg/天）培哚普利的糖尿病LH大鼠，（iii）口服高剂量（1mg/kg/天）培哚普利相同持续时间的类似大鼠，以及（iv）用肼屈嗪、氢氯噻嗪和利血平（分别为75、15和0.75mg/kg/天）三联疗法方案治疗相同持续时间的类似大鼠。
LH大鼠新生期给予链脲佐菌素增加了非空腹血糖并诱导了明显的葡萄糖不耐受，同时伴有血压、血浆胆固醇和尿蛋白排泄的进一步增加。没有一种治疗能够改变糖尿病LH大鼠的葡萄糖耐量。低剂量的培哚普利在预防糖尿病LH大鼠的高血压、血脂异常和蛋白尿方面无效，而高剂量的培哚普利使血压正常化、降低了血浆脂质并减少了蛋白尿。然而，尽管血压显著降低，三联疗法未能改善血脂异常和蛋白尿；相反，该疗法使这两种情况恶化。
在糖尿病LH大鼠中，只有ACE抑制对肾脏和血脂异常有益，从而表明抗高血压方案在糖尿病环境中保护靶器官和脂质代谢的能力可能不同。
