大鼠穹隆下器官注射肾上腺髓质素抑制近端肾小管Na^+,K^+-ATPase活性(英文)

Administration of adrenomedullin into subfornical organ inhibits Na^+,K^+-ATPase activity in single proximal renal tubule of rats

本文旨在观察大鼠穹隆下器(subfornical organ,SFO)注射肾上腺髓质素(adrenomedullin,ADM)对肾小管Na+,K+-ATPase活性的影响。经埋植的导管将ADM0.1μL(20ng/μL)注射到麻醉大鼠SFO。采集血样,以放射免疫法检测血浆ADM和血清内源性地高辛样因子(endogenous digoxin-like factor,EDLF)水平;通过膀胱插管收集动物尿液,采用火焰分光光度法测定尿钠浓度;摘取肾脏,体视显微镜下手工分离单根近端肾小管,用液闪法测定其Na+,K+-ATPase活性。此外,将正常大鼠的近端小管与接受过SFO注射ADM的大鼠血清共同孵育后,检测其Na+,K+-ATPase活性。结果显示,大鼠的尿量和尿钠排出量均在SFO注射ADM后30min达到高峰,在注射后60min仍然保持较高水平(P<0.01)。在SFO注射ADM后30min,近端小管Na+,K+-ATPase活性显著降低(P<0.01),血清EDLF水平显著升高(P<0.01),而血浆ADM水平无显著变化。正常大鼠的近端小管与接受过SFO注射ADM的大鼠血清共同孵育后,其Na+,K+-ATPase活性也显著降低(P<0.01)。以上结果提示,继发于SFO注射ADM的利尿和尿钠排泄反应可能与肾小管Na+,K+-ATPase活性抑制有关;而肾小管Na+,K+-ATPase活性抑制则与SFO注射ADM后血清EDLF水平的升高有关。

The present study was designed to investigate the effect of administration of adrenomedullin （ADM） into subfornical organ （SFO） on renal tubular Na^＋,K^＋ -ATPase activity in rats. Rats under anesthesia were injected with ADM 0.1 μL （20 ng/gtL） via an implanted cannula into SFO （n=6）. Plasma ADM and serum endogenous digitalis-like factor （EDLF） levels were assayed with radioimmunoassay, and urine samples were collected via a canoula intubated in bladder. Urinary sodium concentration was assayed with flame spectrophotometry. Single proximal renal tubule segments were obtained by hand under stereomicroscope and its Na^＋,K^＋ -ATPase activity was measured by liquid scintillation counting. In addition, single proximal renal tubule segments from normal rats （n=6） were incubated with serum from animals administered with ADM into SFO, and then the Na^＋,K^＋ -ATPase activity was determined. The results showed that both urinary volume and sodium excretion amounted to the peak value at 30 rain after ADM administration, and sustained a significant high level at 60 min （P〈0.01）. At 30 rain after ADM administration, there was a significant increase in serum EDLF and a decrease in Na^＋,K^＋ -ATPase activity of proximal tubule （P〈0.01, respectively）, but not in plasma ADM level. Na^＋,K^＋ -ATPase activity was decreased significantly in single proximal renal tubule segments from normal rats incubated with serum from rats administered with ADM into SFO （P〈0.01）. These results suggest that the diuretic and natriuretic responses following administration of ADM into SFO are associated with the inhibition of renal tubule Na^＋,K^＋ -ATPase activity. The inhibition of renal tubule Na^＋,K^＋ -ATPase activity is related to the increase in the serum level of EDLF.