Demeilliers B, Jover B, Mimran A
Groupe Rein et Hypertension, Centre Hospitalier Universitaire, Montpellier, France.
J Hypertens. 1998 Jul;16(7):1023-9. doi: 10.1097/00004872-199816070-00017.
To compare the effects of chronic administrations of the angiotensin II antagonist losartan and of the angiotensin I converting enzyme inhibitor enalapril on renal function in sodium-depleted rats with one-kidney, one clip hypertension, and to examine the contribution of endogenous kinins to the effect of enalapril.
We administered enalapril and losartan (10 and 30 mg/kg per day, respectively) for 6 days to hypertensive rats that had been subjected to dietary sodium-intake restriction for 6 days prior to treatment and continued to be subjected to this restriction during treatment. In an additional group, administration of enalapril was combined with infusion of the bradykinin B2-receptor antagonist Hoe 140 (300 microg/kg per day subcutaneously via an osmotic pump). Renal function of anesthetized rats was assessed by using a clearance technique.
Despite there being similar falls in arterial pressure, glomerular filtration rate (867 +/- 40 microl/min per g kidney weight in untreated rats) was decreased to a larger extent in enalapril-treated than it was in losartan-treated rats (284 +/- 29 versus 438 +/- 36 microl/min per g kidney weight, P < 0.01). Although infusion of Hoe 140 had no influence on the effect of enalapril on arterial pressure, the level of glomerular filtration achieved in rats of this group (545 +/- 55 microl/min per g kidney weight) was similar to that found in losartan-treated rats. No effect of either treatment on renal plasma flow was detected; as a consequence, the excessive decrease in filtration fraction observed for rats in the enalapril-treated group was corrected by concomitant administration of Hoe 140. Interestingly, administration of enalapril resulted in a greater loss of sodium than did administration of losartan (723 +/- 147 versus 308 +/- 57 micromol during 6 days), and this effect was abolished by infusion of Hoe 140 (353 +/- 42 micromol during 6 days).
Administration of enalapril to sodium-depleted rats with one-kidney, one clip hypertension reduces their glomerular filtration rate to a greater extent than does administration of losartan despite these agents having similar effects on systemic blood pressure. Combined administration of enalapril and Hoe 140 has a less marked effect on glomerular filtration rate than does that of enalapril alone. This suggests that kinins play a role in the regulation of efferent arteriolar tone in this rat model.
比较长期给予血管紧张素II拮抗剂氯沙坦和血管紧张素I转换酶抑制剂依那普利对单肾单夹高血压且钠缺乏大鼠肾功能的影响，并研究内源性激肽在依那普利作用中的贡献。
对高血压大鼠分别给予依那普利和氯沙坦（分别为每天10和30mg/kg），共6天。这些大鼠在治疗前已进行6天的饮食钠摄入限制，治疗期间继续维持该限制。在另一组中，依那普利给药与缓激肽B2受体拮抗剂Hoe 140（每天300μg/kg，通过渗透泵皮下注射）输注相结合。采用清除技术评估麻醉大鼠的肾功能。
尽管动脉压下降程度相似，但依那普利治疗组大鼠的肾小球滤过率（未治疗大鼠为867±40μl/min per g肾重）下降幅度大于氯沙坦治疗组（分别为284±29和438±36μl/min per g肾重，P<0.01）。虽然输注Hoe 140对依那普利的动脉压作用无影响，但该组大鼠的肾小球滤过水平（545±55μl/min per g肾重）与氯沙坦治疗组相似。未检测到两种治疗对肾血浆流量的影响；因此，依那普利治疗组大鼠观察到的滤过分数过度下降通过同时给予Hoe 140得到纠正。有趣的是，依那普利给药导致的钠丢失比氯沙坦给药更多（6天内分别为723±147和308±57μmol），而输注Hoe 140消除了这种作用（6天内为353±42μmol）。
对于单肾单夹高血压且钠缺乏的大鼠，尽管依那普利和氯沙坦对全身血压有相似作用，但依那普利给药比氯沙坦给药更能降低其肾小球滤过率。依那普利与Hoe 140联合给药对肾小球滤过率的影响比单独使用依那普利时更不明显。这表明激肽在该大鼠模型中出球小动脉张力调节中起作用。
