SODIUM EXCESS AGGRAVATES HYPERTENSION AND RENAL PARENCHYMAL INJURY IN RATS WITH CHRONIC NO INHIBITION
SODIUM EXCESS AGGRAVATES HYPERTENSION AND RENAL PARENCHYMAL INJURY IN RATS WITH CHRONIC NO INHIBITION
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DOI：
10.1152/ajprenal.1994.266.5.f697
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发表时间：
1994-05-01
影响因子：
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通讯作者：
ZATZ, R
中科院分区：
文献类型：
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作者：
FUJIHARA, CK;MICHELLAZZO, SM;ZATZ, R
慢性一氧化氮（NO）抑制促进高血压和缺血性肾小球损伤，仅伴有轻微肾小球硬化（GS）。我们评估了叠加盐超载的影响，这已被证明会加重GS在其他模型。用NO抑制剂N-ω-硝基-L-精氨酸甲酯（L-NAME）治疗15天，促进了显著的动脉和肾小球高血压、低肾素血症和轻微的肾间质扩张，但没有肾小球损伤。盐超载轻微加重全身和肾小球高血压，促进蛋白尿，间质扩张和肾小球缺血，并矛盾地逆转低肾素血症。血管紧张素II抑制剂氯沙坦减轻肾小球和全身性高血压，并防止这些大鼠的肾损伤。用L-NAME治疗30天导致显著的高血压、高肾素血症、间质扩张和肾小球缺血。伴随的盐超负荷加重了高血压、间质扩张和缺血，并促进了大量蛋白尿、GS和肌酐潴留。氯沙坦可减弱这些作用。钠超负荷加重了慢性NO抑制的肾脏和全身后果，其机制可能包括肾素分泌的反常激活。在该模型中，肾损伤的主要形式是间质扩张和肾小球缺血，而不是GS。
Chronic nitric oxide (NO) inhibition promotes hypertension and ischemic glomerular injury with only minor glomerulosclerosis (GS). We evaluated the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) promoted marked arterial and glomerular hypertension, hyporeninemia, and slight renal interstitial expansion, but no glomerular injury. Salt overload slightly exacerbated systemic and glomerular hypertension, promoted albuminuria, interstitial expansion, and glomerular ischemia, and paradoxically reversed hyporeninemia. The angiotensin II inhibitor losartan attenuated glomerular and systemic hypertension and prevented renal injury in these rats. Thirty days of treatment with L-NAME resulted in marked hypertension, hyperreninemia, interstitial expansion, and glomerular ischemia. Concomitant salt overload exacerbated hypertension, interstitial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overload aggravates the renal and systemic consequences of chronic NO inhibition by mechanisms that may include paradoxical activation of renin secretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model.