Jespersen B, Eiskjaer H, Jensen J D, Mogensen C E, Sørensen S S, Pedersen E B
Department of Medicine and Nephrology C, Skejby Hospital, University Hospital at Aarhus, Denmark.
Scand J Clin Lab Invest. 1995 Jul;55(4):273-87. doi: 10.3109/00365519509104964.
To elucidate and to try to reverse the antinatriuretic mechanisms in liver cirrhosis, atrial natriuretic peptide (ANP) was given as a pharmacological bolus dose (2 micrograms per kg body weight) to 14 cirrhotic patients, and as a control to 14 healthy subjects. The nine patients with ascites had baseline values of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure (BP) similar to controls. Their distal tubular fractional reabsorption of sodium (DFRNa), estimated by the lithium clearance technique, was higher than in controls, and so were plasma values of aldosterone (564 vs. 119 pmol l-1 medians), endothelin (1.23 vs. 0.63 pmol l-1), ANP (7.5 vs. 3.6 pmol l-1) and cyclic GMP (8.8 vs. 4.6 nmol l-1); p < 0.01 for all. The five patients without ascites had higher GFR and ERPF, and lower plasma angiotensin II than controls. After ANP injection, similar plasma levels of ANP and cyclic GMP were reached in all groups. Urinary sodium excretion rate increased in controls (0.23 to 0.52 mmol min-1, p < 0.01), while GFR increased (108 to 117 ml min-1, p < 0.05), and DFRNa decreased (93 to 89%, p < 0.01). In cirrhotics with ascites sodium excretion was unaltered (0.12 to 0.11 mmol min-1), and so was GFR (84 to 83 ml min-1). Proximal tubular fractional reabsorption of sodium increased after 90 min, whereas DFRNa decreased immediately (97 to 96%, p < 0.01) though less markedly than in controls. Sodium excretion increased in four of five patients without ascites (0.23 to 0.27 mmol min-1, medians). In patients with ascites, endothelin in plasma decreased after ANP (p < 0.05). Plasma levels of angiotensin II, aldosterone and vasopressin were unchanged in all groups. In conclusion, although hyper-reabsorption of sodium occurred in the distal rather than the proximal part of the nephron in cirrhotic patients with ascites, ANP had no natriuretic effect. This was most probably due primarily to the lack of increase of GFR and blunted inhibition of DFRNa, attributed to high aldosterone. The effect of ANP in suppressing the high endothelin did not seem to improve sodium excretion.
为阐明并试图逆转肝硬化中的利钠拮抗机制，对14例肝硬化患者给予心房利钠肽（ANP）药理学推注剂量（每千克体重2微克），并以14名健康受试者作为对照。9例腹水患者的肾小球滤过率（GFR）、有效肾血浆流量（ERPF）和血压（BP）基线值与对照组相似。通过锂清除技术估算，他们的远端肾小管钠分数重吸收（DFRNa）高于对照组，醛固酮（中位数分别为564 vs. 119 pmol/L）、内皮素（1.23 vs. 0.63 pmol/L）、ANP（7.5 vs. 3.6 pmol/L）和环磷酸鸟苷（8.8 vs. 4.6 nmol/L）的血浆值也是如此；所有这些指标的p值均<0.01。5例无腹水患者的GFR和ERPF较高，血浆血管紧张素II低于对照组。注射ANP后，所有组的ANP和环磷酸鸟苷血浆水平相似。对照组尿钠排泄率增加（从0.23至0.52 mmol/min，p<0.01），GFR增加（从108至117 ml/min，p<0.05），DFRNa降低（从93%至89%，p<0.01）。有腹水的肝硬化患者钠排泄未改变（从0.12至0.11 mmol/min），GFR也未改变（从84至83 ml/min）。9０分钟后近端肾小管钠分数重吸收增加，而DFRNa立即降低（从97%至96%，p<0.01），但降低幅度小于对照组。5例无腹水患者中有4例钠排泄增加（中位数从0.23至0.27 mmol/min）。在有腹水的患者中，ANP后血浆内皮素降低（p<0.05）。所有组的血浆血管紧张素II、醛固酮和血管加压素水平均未改变。总之，尽管有腹水的肝硬化患者在肾单位远端而非近端发生钠重吸收增加，但ANP没有利钠作用。这很可能主要是由于GFR未增加以及DFRNa抑制减弱，这归因于高醛固酮水平。ANP抑制高内皮素水平的作用似乎并未改善钠排泄。
