Beutler J J, Koomans H A, Bijlsma J A, Dorhout Mees E J
Department of Nephrology, University Hospital Utrecht, The Netherlands.
J Pharmacol Exp Ther. 1990 Dec;255(3):1314-9.
The hypothesis that the methylxanthine theophylline and atrial natriuretic peptide (ANP) have similar actions in the kidney was tested. Doses of equal natriuretic potency were administered to seven healthy men during maximal water diuresis. Theophylline (1.2 mg/kg/min) increased sodium excretion to 3-fold, increased glomerular filtration rate and filtration fraction and had no effect on estimated renal plasma flow. Increments were also found in maximal urine flow, distal delivery index and fractional lithium clearance. Diluting segment reabsorption index decreased, and minimal urine osmolality increased. ANP, of which the dose was low (0.01 micrograms/kg/min), had similar effects on sodium excretion, glomerular filtration rate, filtration fraction, minimal urine osmolality and diluting segment reabsorption index, but it decreased estimated renal plasma flow and had no effect on distal delivery and fractional lithium clearance. In a third clearance study ANP was infused after 3 days of treatment with theophylline. The only difference observed was that theophylline prevented the ANP-induced fall in estimated renal plasma flow. Theophylline did not enhance the natriuretic effect of ANP nor its effect to stimulate urinary cyclic guanosine monophosphate. Pretreatment with theophylline had raised plasma renin activity, but the effect of ANP to lower plasma renin activity was not diminished. Our observations agree with the idea that theophylline and ANP act via common mechanisms in the kidney. However, ANP effects are independent of theophylline's action.
对甲基黄嘌呤类药物茶碱和心钠素（ANP）在肾脏中具有相似作用这一假说进行了验证。在最大水利尿期间，给7名健康男性给予了等利钠效能的剂量。茶碱（1.2毫克/千克/分钟）使钠排泄增加至3倍，增加了肾小球滤过率和滤过分数，对估计的肾血浆流量无影响。最大尿流、远端输送指数和锂清除分数也有所增加。稀释段重吸收指数降低，最小尿渗透压增加。剂量较低（0.01微克/千克/分钟）的心钠素对钠排泄、肾小球滤过率、滤过分数、最小尿渗透压和稀释段重吸收指数有相似的作用，但它降低了估计的肾血浆流量，对远端输送和锂清除分数无影响。在第三项清除率研究中，在茶碱治疗3天后输注心钠素。观察到的唯一差异是，茶碱可防止心钠素引起的估计肾血浆流量下降。茶碱既未增强心钠素的利钠作用，也未增强其刺激尿中环磷酸鸟苷的作用。茶碱预处理可提高血浆肾素活性，但心钠素降低血浆肾素活性的作用并未减弱。我们的观察结果与茶碱和心钠素在肾脏中通过共同机制起作用的观点一致。然而，心钠素的作用独立于茶碱的作用。
