Hulthén U L, Cao Z, Rumble J R, Cooper M E, Johnston C I
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Am J Hypertens. 1996 Sep;9(9):895-901. doi: 10.1016/s0895-7061(96)00177-x.
The aim of this study was to compare the effects of angiotensin converting enzyme (ACE) inhibition, angiotensin II (AII) AT1-receptor blockade, and dihydropyridine calcium antagonism on hypertrophy and on vascular albumin permeability in kidney, heart, and mesenteric artery in a model combining genetic hypertension and diabetes mellitus. Diabetes mellitus was induced by streptozotocin in 8-week-old spontaneously hypertensive rats. The animals were randomized to receive no treatment, the angiotensin converting enzyme inhibitor ramipril, the AII AT1-receptor blocker valsartan, or the dihydropyridine calcium antagonist lacidipine for 3 weeks. Vascular albumin permeability was measured as the tissue content of intravenously injected Evans blue dye (EB) in kidney, heart, and mesenteric artery and the tissue/plasma EB ratio was calculated. Systolic blood pressure was reduced by all three antihypertensive regimens. Glycemic control was similar in all diabetic groups. Kidney hypertrophy was not affected by any of the antihypertensive drugs. Hypertrophy of the mesenteric artery was enhanced by lacidipine but was not affected by ramipril or valsartan. Relative heart weight was also increased by lacidipine. Vascular albumin permeability, expressed as EB content in micrograms/gram dry weight or as tissue/plasma EB ratio, was higher in the kidneys of lacidipine-treated rats than in any other group of diabetic rats. There was a positive correlation between kidney weight/body weight and kidney/plasma EB ratio in the diabetic rats. These findings indicate that the dihydropyridine calcium antagonist lacidipine is associated with an unfavorable effect on vascular hypertrophy and on vascular albumin permeability in the kidneys in rats with hypertension and diabetes mellitus. Furthermore, there seems to be a coupling in the diabetic kidney between hypertrophy and increased vascular albumin permeability.
本研究的目的是在一个合并遗传性高血压和糖尿病的模型中，比较血管紧张素转换酶（ACE）抑制、血管紧张素II（AII）AT1受体阻断以及二氢吡啶类钙拮抗作用对肾脏、心脏和肠系膜动脉肥大及血管白蛋白通透性的影响。通过链脲佐菌素诱导8周龄自发性高血压大鼠患糖尿病。将动物随机分为未治疗组、血管紧张素转换酶抑制剂雷米普利组、AII AT1受体阻滞剂缬沙坦组或二氢吡啶类钙拮抗剂拉西地平组，治疗3周。通过测定静脉注射伊文思蓝染料（EB）在肾脏、心脏和肠系膜动脉中的组织含量来测量血管白蛋白通透性，并计算组织/血浆EB比值。所有三种降压方案均降低了收缩压。所有糖尿病组的血糖控制情况相似。任何一种降压药物均未影响肾脏肥大。拉西地平增强了肠系膜动脉的肥大，但雷米普利或缬沙坦未对其产生影响。拉西地平也增加了相对心脏重量。以微克/克干重表示的EB含量或组织/血浆EB比值所衡量的血管白蛋白通透性，在接受拉西地平治疗的大鼠肾脏中高于其他任何糖尿病大鼠组。糖尿病大鼠的肾脏重量/体重与肾脏/血浆EB比值之间存在正相关。这些发现表明，二氢吡啶类钙拮抗剂拉西地平对高血压和糖尿病大鼠的肾脏血管肥大及血管白蛋白通透性有不良影响。此外，在糖尿病肾脏中，肥大与血管白蛋白通透性增加之间似乎存在关联。
