Baylis C
Department of Physiology, West Virginia University Health Sciences Center, Morgantown.
Am J Kidney Dis. 1993 Dec;22(6):842-50. doi: 10.1016/s0272-6386(12)70344-x.
Studies of conscious, chronically catheterized, young (3 to 5 months of age) and old (19 to 22 months of age) male Sprague Dawley rats in the baseline state showed that glomerular filtration rate (factored for body weight) was lower and urine flow higher in old compared with young rats. Acute blockade of endogenous angiotensin II (AII) with either converting enzyme inhibitor (CEI) or Losartan (Dupont Merck, Wilmington, DE) caused small variable decreases in blood pressure in both age groups and produced a significant renal vasodilation with increases in renal plasma flow in the older rats. In separate studies using low-dose AII infusion (5 ng/kg body weight/min), an increase in filtration fraction was the only effect seen in both young and old rats with an intact renin/AII system; no effect was seen with CEI. During high-dose AII (20 ng/kg body weight/min), significant and similar increases were seen in blood pressure and renal vascular resistance in old and young rats, and the patterns of blood pressure and renal hemodynamic responses were similar with and without acute CEI. A natriuretic and diuretic response to high-dose AII was seen in young rats with intact endogenous renin/AII, whereas old rats were completely refractory to this action of AII. Against a background of acute CEI, no natriuretic/diuretic response to high-dose AII was seen in either age group. Thus, in the baseline state, renal hemodynamics in the old kidney are controlled by endogenous AII since CEI and Losartan produce renal vasodilation in old but not young rats.(ABSTRACT TRUNCATED AT 250 WORDS)
对清醒、长期插有导管的年轻(3至5个月龄)和老年(19至22个月龄)雄性Sprague Dawley大鼠在基础状态下的研究表明,与年轻大鼠相比,老年大鼠的肾小球滤过率(按体重折算)较低,尿流量较高。用转化酶抑制剂(CEI)或氯沙坦(杜邦默克公司,特拉华州威尔明顿)急性阻断内源性血管紧张素II(AII),两个年龄组的血压均出现小幅度的可变下降,并且老年大鼠出现显著的肾血管舒张,肾血浆流量增加。在使用低剂量AII输注(5 ng/kg体重/分钟)的单独研究中,在肾素/AII系统完整的年轻和老年大鼠中,唯一观察到的效应是滤过分数增加;CEI对此无影响。在高剂量AII(20 ng/kg体重/分钟)期间,老年和年轻大鼠的血压和肾血管阻力均出现显著且相似的增加,无论有无急性CEI,血压和肾血流动力学反应模式均相似。在具有完整内源性肾素/AII的年轻大鼠中,观察到对高剂量AII的利钠和利尿反应,而老年大鼠对AII的这种作用完全无反应。在急性CEI的背景下,两个年龄组对高剂量AII均未观察到利钠/利尿反应。因此,在基础状态下,老年肾脏的肾血流动力学受内源性AII控制,因为CEI和氯沙坦在老年大鼠而非年轻大鼠中产生肾血管舒张。(摘要截短至250字)