Rathaus M, Podjarny E, Pomeranz A, Bernheim J
Department of Nephrology, Meir Hospital, Kfar Saba, Israel.
Am J Physiol. 1990 Feb;258(2 Pt 2):F382-7. doi: 10.1152/ajprenal.1990.258.2.F382.
Captopril stimulates glomerular prostaglandin (PG) synthesis and increases glomerular filtration rate (GFR) in Na-repleted rats, whereas, in Na-depleted rats, it fails to stimulate PG synthesis and decreases GFR. In the present work the influence of chronic and acute NaCl loading on PG synthesis and renal function was studied in Na-depleted rats receiving captopril (LNC rats). Glomerular PGE2 and 6-keto-PGF1 alpha were not increased in LNC rats and were significantly lower than in Na-depleted rats (LN). Na repletion, while continuing captopril, increased PG synthesis above control levels. Addition of captopril in vitro to the incubation medium stimulated PGE2 synthesis in glomeruli of control rats, whereas it depressed it in LN rats. Acute loading with NaCl in LNC rats increased inulin and PAH clearances to values significantly greater than in control rats and similar to those of normal rats receiving captopril. Comparable volume loading with isotonic mannitol or 3% albumin increased inulin and PAH clearances only to control values. The specific effect of NaCl in acute loading was prevented by cyclooxygenase inhibition and was not mediated by increased systemic blood pressure. The results provide evidence that the effects of captopril on glomerular PG synthesis and renal function depend on the state of Na balance.
卡托普利可刺激钠充足大鼠的肾小球前列腺素（PG）合成并增加肾小球滤过率（GFR），而在钠缺乏大鼠中，它无法刺激PG合成且会降低GFR。在本研究中，对接受卡托普利治疗的钠缺乏大鼠（LNC大鼠）进行了慢性和急性氯化钠负荷对PG合成及肾功能影响的研究。LNC大鼠的肾小球PGE2和6-酮-PGF1α未增加，且显著低于钠缺乏大鼠（LN）。在持续给予卡托普利的同时补充钠，可使PG合成增加至高于对照水平。体外向孵育培养基中添加卡托普利可刺激对照大鼠肾小球的PGE2合成，而在LN大鼠中则抑制其合成。LNC大鼠急性给予氯化钠负荷后，菊粉和对氨基马尿酸清除率增加至显著高于对照大鼠的值，且与接受卡托普利治疗的正常大鼠相似。用等渗甘露醇或3%白蛋白进行的同等容量负荷仅使菊粉和对氨基马尿酸清除率增加至对照值。急性负荷时氯化钠的特定作用可被环氧化酶抑制所阻断，且不受全身血压升高的介导。结果表明，卡托普利对肾小球PG合成和肾功能的影响取决于钠平衡状态。
