Mauran P, Pham I, Sediame S, Jolly D, Chabrier P E, Carayon A, Andrivet P, Adnot S
Département de Physiologie de la Faculté de Médecine de Reims et American Memorial Hospital, France.
J Cardiovasc Pharmacol. 1998 May;31(5):669-76. doi: 10.1097/00005344-199805000-00004.
To investigate the role of atrial natriuretic factor (ANF) in renal responses to a decrease in central blood volume, we examined the effects of ANF infusion on renal function and hormones during prolonged lower-body negative pressure (LBNP). Ten healthy volunteers participated in two experimental sequences, each comprising a 120-min baseline period followed by the application of -20 mm Hg LBNP for 90 min. During one of the two sequences, ANF was infused throughout LBNP application at the constant rate of 2.5 ng/kg/min. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by using inulin and p-aminohippuric acid clearance techniques. LBNP induced a significant decrease in ERPF (534 +/- 28 to 457 +/- 26 ml/min; p < 0.05), GFR (120 +/- 2.5 to 112 +/- 2.5 ml/min; p < or = 0.01), in urine excretion (12 +/- 0.9 to 5.6 +/- 0.5 ml/min; p < 0.001), in sodium excretion (0.36 +/- 0.03 to 0.30 +/- 0.02 mmol/min; p < 0.05), and in plasma ANF (19 +/- 3 to 11 +/- 2 pg/ml; p = 0.001) concomitant with an increase in plasma renin activity (PRA; 0.48 +/- 0.09 to 0.87 +/- 0.16 ng/ml/h; p = 0.01) and of forearm vascular resistance (FVR; p < 0.05). The combination of ANF infusion with LBNP led to a slight increase in plasma ANF from baseline (from 20 +/- 2 to 28 +/- 3 pg/ml; p < 0.05). Compared with values obtained during LBNP with saline vehicle infusion, values obtained during LBNP with ANF infusion were similar for ERPF (463 +/- 23 vs. 457 +/- 26 ml/min), for GFR (111 +/- 2 vs. 112 +/- 2 ml/min), and for urine excretion (7 +/- 0.6 vs. 5.6 +/- 0.5 ml/min; p = 0.07), but greater for fractional excretion of sodium (2.38 +/- 0.25% vs. 1.91 +/- 0.11%; p < 0.05) and FVR (p < 0.05), and smaller for PRA (0.49 +/- 0.1 vs. 0.87 +/- 0.16 ng/ml/h; p < 0.01). These data show that ANF infusion attenuates the antinatriuretic effect of low-level LBNP and its PRA-increasing effects without altering renal hemodynamic responses to LBNP, although there is a decrease in the LBNP-induced forearm vasoconstriction. These results were obtained with plasma ANF levels slightly higher than those in baseline. They support the hypothesis that a decrease in ANF secretion might contribute to the antinatriuretic effect of LBNP.
为研究心房利钠因子(ANF)在肾脏对中心血容量减少反应中的作用,我们检测了在长时间下体负压(LBNP)期间输注ANF对肾功能和激素的影响。10名健康志愿者参与了两个实验序列,每个序列包括120分钟的基线期,随后施加-20 mmHg的LBNP 90分钟。在两个序列中的一个期间,在整个LBNP施加过程中以2.5 ng/kg/分钟的恒定速率输注ANF。采用菊粉和对氨基马尿酸清除技术测量肾小球滤过率(GFR)和有效肾血浆流量(ERPF)。LBNP导致ERPF显著降低(从534±28降至457±26 ml/分钟;p<0.05)、GFR降低(从120±2.5降至112±2.5 ml/分钟;p≤0.01)、尿排泄降低(从12±0.9降至5.6±0.5 ml/分钟;p<0.001)、钠排泄降低(从0.36±0.03降至0.30±0.02 mmol/分钟;p<0.05)以及血浆ANF降低(从19±3降至11±2 pg/ml;p = 0.001),同时血浆肾素活性(PRA)升高(从0.48±0.09升至0.87±0.16 ng/ml/小时;p = 0.01)以及前臂血管阻力(FVR)升高(p<0.05)。ANF输注与LBNP联合导致血浆ANF较基线略有升高(从20±2升至28±3 pg/ml;p<0.05)。与输注生理盐水载体的LBNP期间获得的值相比,输注ANF的LBNP期间获得的ERPF值(463±23对457±26 ml/分钟)、GFR值(111±2对112±2 ml/分钟)和尿排泄值(7±0.6对5.6±0.5 ml/分钟;p = 0.07)相似,但钠分数排泄(2.38±0.25%对1.91±0.11%;p<0.05)和FVR更高(p<0.05),而PRA更低(0.49±0.1对0.87±0.16 ng/ml/小时;p<0.01)。这些数据表明,输注ANF可减弱低水平LBNP的利钠作用及其PRA升高作用,而不改变肾脏对LBNP的血流动力学反应,尽管LBNP诱导的前臂血管收缩有所降低。这些结果是在血浆ANF水平略高于基线水平时获得的。它们支持以下假设,即ANF分泌减少可能有助于LBNP的利钠作用。