Ohanian J, Young M A, Shen Y T, Gaivin R, Vatner S F, Graham R M
Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston.
Am J Physiol. 1989 Oct;257(4 Pt 2):F565-73. doi: 10.1152/ajprenal.1989.257.4.F565.
We studied the effects of 30-min infusions of the synthetic 25-amino acid atrial natriuretic factor [ANF-(102-126)] and the 28-amino acid ANF-(99-126) at 0.1 and 0.3 micrograms.kg-1.min-1 on urine flow rate, sodium excretion, and arterial pressure in conscious dogs. Each dose was administered on a separate day following a 1-h stabilization period. We also compared the effects of 60-min infusions of ANF, 0.01 micrograms.kg-1.min-1, or water infusion on separate days in conscious dogs. Arterial pressure was reduced in a dose-dependent fashion, reaching statistical significance at a dose of 0.3 micrograms.kg-1.min-1. During the 0.01-micrograms.kg-1.min-1 infusion, the plasma concentration of ANF rose approximately threefold (from 68 +/- 7 to 207 +/- 14 pg/ml), with no change in urine flow rate, sodium excretion, or arterial pressure. At a dose of 0.1 micrograms.kg-1.min-1, urine flow increased (P less than 0.05) by 0.41 +/- 0.15 ml/min, and sodium excretion rose by 72 +/- 24 mu eq/min, but not significantly, whereas plasma ANF levels rose to 1,236 +/- 229 pg/ml. At the highest dose of ANF (0.3 micrograms.kg-1.min-1) urine flow rose by 0.62 +/- 0.16 ml/min, P less than 0.05, and sodium excretion rose by 139 +/- 30 mu eq/min, P less than 0.05, whereas plasma levels of ANF rose to 2,436 +/- 320 pg/ml. In contrast, volume loading with dextran increased urine flow by 3.5 +/- 1.3 ml/min, P less than 0.05, and sodium excretion by 439 +/- 147 mu eq/min, P less than 0.05, whereas ANF rose to only 320 +/- 69 pg/ml. These results suggest that, in the conscious dog, ANF does not cause significant diuretic or natriuretic effects until plasma levels are markedly above those observed in physiological conditions. A possible explanation for the difference between this and previous studies is that the renal effects of ANF, at physiological plasma levels, are indirect and thus dependent on autonomic and hormonal (angiotensin, vasopressin, and aldosterone levels) factors governing the renal function of the animal.
我们研究了以0.1和0.3微克·千克⁻¹·分钟⁻¹的剂量静脉输注30分钟合成的25个氨基酸的心房利钠因子[ANF-(102 - 126)]和28个氨基酸的ANF-(99 - 126)对清醒犬尿流率、钠排泄及动脉血压的影响。每个剂量在1小时稳定期后的不同日期给予。我们还比较了在清醒犬的不同日期分别静脉输注60分钟ANF（0.01微克·千克⁻¹·分钟⁻¹）或输注生理盐水的效果。动脉血压呈剂量依赖性降低，在剂量为0.3微克·千克⁻¹·分钟⁻¹时达到统计学显著水平。在输注0.01微克·千克⁻¹·分钟⁻¹期间，ANF的血浆浓度升高约三倍（从68±7升至207±14皮克/毫升），而尿流率、钠排泄或动脉血压无变化。在剂量为0.1微克·千克⁻¹·分钟⁻¹时，尿流增加（P＜0.05），增加了0.41±0.15毫升/分钟，钠排泄增加了72±24微当量/分钟，但无统计学显著差异，而血浆ANF水平升至1236±229皮克/毫升。在ANF的最高剂量（0.3微克·千克⁻¹·分钟⁻¹）时，尿流增加了0.62±0.16毫升/分钟，P＜0.05，钠排泄增加了139±30微当量/分钟，P＜0.05，而血浆ANF水平升至2436±320皮克/毫升。相比之下，用右旋糖酐扩容使尿流增加了3.5±1.3毫升/分钟，P＜0.05，钠排泄增加了439±147微当量/分钟，P＜0.05，而ANF仅升至320±69皮克/毫升。这些结果表明，在清醒犬中，直到血浆水平明显高于生理状态下观察到的水平，ANF才会引起显著的利尿或利钠作用。对此与先前研究差异的一种可能解释是，在生理血浆水平时，ANF的肾脏效应是间接的，因此依赖于控制动物肾功能的自主神经和激素（血管紧张素、血管升压素和醛固酮水平）因素。
