Guron G, Adams M A, Sundelin B, Friberg P
Department of Physiology, Institute of Physiology and Pharmacology, Göteborg, Sweden.
Hypertension. 1997 Jan;29(1 Pt 1):91-7. doi: 10.1161/01.hyp.29.1.91.
Recently, we reported that neonatal blockade of the renin-angiotensin system in the rat produces irreversible abnormalities in renal histology associated with increased diuresis. In the present study, we assessed the long-term consequences of neonatal angiotensin-converting enzyme inhibition on renal function. Rats were injected with 10 mg.kg-1.d-1 enalapril or vehicle from day 3 to day 24 after birth. Urine concentrating ability, renal function, and renal histology were assessed in 16-week-old rats. There was a twofold increase in diuresis and water intake in enalapril-treated rats throughout the study course. Urine osmolality after 24 hours of water deprivation was 1008 +/- 108 and 2549 +/- 48 mOsm.kg-1 (P < .05) in enalapril- and vehicle-treated rats, respectively. Glomerular filtration rate (0.54 +/- 0.03 versus 0.75 +/- 0.06 mL.min-1x100 g body wt-1, P < .05) and effective renal plasma flow (1.76 +/- 0.09 versus 2.19 +/- 0.14 mL.min-1x100 g body wt-1, P < .05) were reduced in neonatally enalapril-treated versus control rats. Absolute and fractional urinary sodium excretion values were elevated (P < .05) in enalapril-treated rats. Semiquantitative assessment of renal histology demonstrated statistically significant degrees of papillary atrophy, interstitial fibrosis and inflammation, tubular atrophy and dilatation, and focal glomerulosclerosis in neonatally enalapril-treated rats. In conclusion, neonatal angiotensin-converting enzyme inhibition in the rat produces irreversible alterations in renal function and morphology, demonstrating the importance of an intact renin-angiotensin system neonatally for normal renal development.
最近，我们报道了新生大鼠肾素 - 血管紧张素系统的阻断会导致肾脏组织学出现不可逆异常，并伴有多尿增加。在本研究中，我们评估了新生期血管紧张素转换酶抑制对肾功能的长期影响。从出生后第3天至第24天，给大鼠注射10mg·kg⁻¹·d⁻¹的依那普利或赋形剂。对16周龄大鼠的尿液浓缩能力、肾功能和肾脏组织学进行评估。在整个研究过程中，依那普利治疗的大鼠的尿量和饮水量增加了两倍。禁水24小时后，依那普利治疗组和赋形剂治疗组大鼠的尿渗透压分别为1008±108和2549±48mOsm·kg⁻¹（P<.05）。新生期接受依那普利治疗的大鼠与对照大鼠相比，肾小球滤过率（0.54±0.03对0.75±0.06mL·min⁻¹×100g体重⁻¹，P<.05）和有效肾血浆流量（1.76±0.09对2.19±0.14mL·min⁻¹×100g体重⁻¹，P<.05）降低。依那普利治疗的大鼠的绝对和分数尿钠排泄值升高（P<.05）。肾脏组织学的半定量评估显示，新生期接受依那普利治疗的大鼠出现了具有统计学意义的乳头萎缩、间质纤维化和炎症、肾小管萎缩和扩张以及局灶性肾小球硬化。总之，新生大鼠血管紧张素转换酶抑制会导致肾功能和形态发生不可逆改变，表明新生期完整的肾素 - 血管紧张素系统对正常肾脏发育至关重要。
