Fujihara C K, Michellazzo S M, de Nucci G, Zatz R
Department of Clinical Medicine, University of São Paulo School of Medicine, Brazil.
Am J Physiol. 1994 May;266(5 Pt 2):F697-705. doi: 10.1152/ajprenal.1994.266.5.F697.
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.
慢性一氧化氮（NO）抑制可促进高血压和缺血性肾小球损伤，仅伴有轻微的肾小球硬化（GS）。我们评估了叠加盐负荷的影响，在其他模型中已显示盐负荷会加重GS。用NO抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）治疗15天可导致明显的动脉和肾小球高血压、低肾素血症以及轻微的肾间质扩张，但无肾小球损伤。盐负荷会使全身和肾小球高血压稍有加重，促进蛋白尿、间质扩张和肾小球缺血，并且反常地逆转低肾素血症。血管紧张素II抑制剂氯沙坦可减轻这些大鼠的肾小球和全身高血压，并预防肾损伤。用L-NAME治疗30天会导致明显的高血压、高肾素血症、间质扩张和肾小球缺血。同时存在的盐负荷会加重高血压、间质扩张和缺血，并促进大量蛋白尿、GS和肌酐潴留。氯沙坦可减轻这些影响。钠负荷通过可能包括反常激活肾素分泌的机制加重慢性NO抑制的肾脏和全身后果。在该模型中，间质扩张和肾小球缺血而非GS构成肾损伤的主要形式。
