Guron G, Nilsson A, Nitescu N, Nielsen S, Sundelin B, Frøkiaer J, Friberg P
Department of Physiology, Institute of Physiology and Pharmacology, Göteborg University, Sweden.
Acta Physiol Scand. 1999 Jan;165(1):103-12. doi: 10.1046/j.1365-201x.1999.00477.x.
Neonatal angiotensin-converting enzyme inhibition or angiotensin II type-1 receptor blockade induces irreversible renal histological abnormalities and an impaired urinary concentrating ability in the rat. The aim of the present study was to determine the pathophysiological mechanisms underlying the defect in urine concentration in adult rats treated neonatally with enalapril. Male Wistar rats received daily intraperitoneal injections of enalapril (10 mg kg(-1)) or saline vehicle from 3 to 24 days of age. Assessments of fluid handling and maximal urine osmolality (Uosm(max)), renal function and tubular free water reabsorption (T(c)H2O) under pentobarbital anaesthesia, renal tissue solute concentrations, renal aquaporin-2 (AQP2) expression, and kidney histology, were performed in 12-16-week-old rats. Uosm(max) (1488 +/- 109 vs. 2858 +/- 116 mosm kg(-1), P < 0.05) and maximal T(c)H2O were reduced in enalapril- vs. vehicle-treated rats after administration of 1-desamino-8-D-arginine vasopressin. Neonatally enalapril-treated rats showed marked papillary atrophy, a decrease in medullary tissue solute concentrations, and a reduction in AQP2 expression specifically in the inner medulla. Glomerular filtration rate, renal plasma flow and urinary excretion rates of sodium, potassium and chloride did not differ between groups. In conclusion, adult rats treated neonatally with enalapril showed a urinary concentrating defect of renal origin which primarily could be explained by the papillary atrophy. However, an impaired ability to generate medullary interstitial hypertonicity, and a decrease in inner medullary AQP2 expression, also seem to contribute to this defect.
新生儿期血管紧张素转换酶抑制或血管紧张素II 1型受体阻断可导致大鼠出现不可逆的肾脏组织学异常及尿浓缩能力受损。本研究的目的是确定新生期用依那普利治疗的成年大鼠尿浓缩功能缺陷的病理生理机制。雄性Wistar大鼠在3至24日龄时每日腹腔注射依那普利（10 mg kg⁻¹）或生理盐水。对12至16周龄大鼠在戊巴比妥麻醉下进行液体处理和最大尿渗透压（Uosm(max)）、肾功能及肾小管自由水重吸收（T(c)H2O）评估、肾组织溶质浓度、肾水通道蛋白-2（AQP2）表达及肾脏组织学检查。给予1-去氨基-8-D-精氨酸加压素后，依那普利治疗组大鼠的Uosm(max)（1488 ± 109 vs. 2858 ± 116 mosm kg⁻¹，P < 0.05）和最大T(c)H2O降低。新生期接受依那普利治疗的大鼠出现明显的乳头萎缩、髓质组织溶质浓度降低以及AQP2表达特别是在内髓质的减少。两组之间肾小球滤过率、肾血浆流量以及钠、钾和氯的尿排泄率无差异。总之，新生期用依那普利治疗的成年大鼠存在源于肾脏的尿浓缩功能缺陷，这主要可由乳头萎缩来解释。然而，髓质间质高渗形成能力受损以及内髓质AQP2表达降低似乎也促成了这一缺陷。
