De Feo M L, La Villa G, Lazzeri C, Tosti-Guerra C, Becorpi A, Pupilli C, Mannelli M
Department of Clinical Pathophysiology, University of Florence, Italy.
Hypertension. 1997 Jan;29(1 Pt 1):70-4. doi: 10.1161/01.hyp.29.1.70.
To evaluate the functional relationship between cardiac natriuretic peptides and endothelin-1 within the human kidney, we studied the effects exerted by infusion of brain natriuretic peptide on urinary endothelin-1 excretion. We studied twice in a single-blind manner five normal volunteers who received a constant infusion of 5% dextrose (250 mL/h) or human brain natriuretic peptide-32 at a dose of 4 pmol/kg per minute. Blood samples were drawn at intervals for measurement of hematocrit and concentrations of creatinine, electrolytes, brain natriuretic peptide, and endothelin-1. Urine was collected an intervals for measurement of flow rate and concentrations of creatinine, sodium, cGMP, and endothelin-1. Blood pressure and heart rate were measured every 15 minutes. Placebo administration did not change blood pressure, heart rate, or any of the other parameters measured in plasma and urine. As expected, brain natriuretic peptide infusion caused significant increases in its own plasma levels (basal versus peak levels [mean +/- SD], 1.45 +/- 0.20 versus 50.5 +/- 6.0 pmol/L, P < .01), in urinary cGMP (0.75 +/- 0.16 versus 1.92 +/- 0.81 fmol/min, P < .05), and in urinary sodium excretion (140.0 +/- 38.7 versus 624.2 +/- 181.6 mumol/min, P < .01). In addition, it caused an increase in urinary endothelin-1 excretion (4.32 +/- 2.11 versus 19.67 +/- 9.52 fmol/min, P < .05), without modifying plasma endothelin-1, blood pressure, heart rate, creatinine clearance, and urinary flow rate. Our data indicate that brain natriuretic peptide, at plasma levels comparable to those observed in patients with heart failure, causes a significant increase in urinary but not plasma endothelin-1, thus demonstrating a functional link between cardiac natriuretic peptides and renal release of endothelin-1.
为了评估人心肾中利钠肽与内皮素-1之间的功能关系，我们研究了静脉输注脑利钠肽对尿内皮素-1排泄的影响。我们以单盲方式对5名正常志愿者进行了两次研究，这些志愿者接受了5%葡萄糖（250 mL/h）或剂量为4 pmol/kg每分钟的人脑利钠肽-32的持续静脉输注。每隔一段时间采集血样以测定血细胞比容以及肌酐、电解质、脑利钠肽和内皮素-1的浓度。每隔一段时间收集尿液以测定流速以及肌酐、钠、环磷酸鸟苷（cGMP）和内皮素-1的浓度。每15分钟测量一次血压和心率。给予安慰剂未改变血压、心率或血浆和尿液中测量的任何其他参数。正如预期的那样，输注脑利钠肽导致其自身血浆水平显著升高（基础水平与峰值水平[均值±标准差]，1.45±0.20与50.5±6.0 pmol/L，P<.01），尿cGMP升高（0.75±0.16与1.92±0.81 fmol/min，P<.05），以及尿钠排泄增加（140.0±38.7与624.2±181.6 μmol/min，P<.01）。此外，它还导致尿内皮素-1排泄增加（4.32±2.11与19.67±9.52 fmol/min，P<.05），而未改变血浆内皮素-1、血压、心率、肌酐清除率和尿流率。我们的数据表明，在与心力衰竭患者中观察到的血浆水平相当的情况下，脑利钠肽会导致尿内皮素-1显著增加，但不会导致血浆内皮素-1增加，从而证明了利钠肽与肾源性内皮素-1释放之间的功能联系。
