Miyamori I, Ikeda M, Matsubara T, Okamoto S, Koshida H, Yasuhara S, Morise T, Takeda R
Br J Clin Pharmacol. 1987 Apr;23(4):425-31. doi: 10.1111/j.1365-2125.1987.tb03071.x.
The renal, cardiovascular and hormonal effects of intravenous infusion of alpha-human atrial natriuretic polypeptides (alpha-hANP) at the concentrations of 0.0125, 0.025, 0.05, 0.1 microgram kg-1 min-1 for 20 min was studied in six male volunteers before and after indomethacin administration (150 mg day-1, three times daily for 3 days). Dose-dependent diuresis and natriuresis were observed in all subjects between the concentrations of 0.025 and 0.1 microgram kg-1 min-1, which were not influenced by indomethacin. Diastolic blood pressure decreased significantly (P less than 0.05) at the higher dose (0.05 microgram kg-1 min-1) of alpha-hANP, which was attenuated by indomethacin pretreatment. The plasma concentration of the immunoreactive alpha-hANP was 73.7 +/- 25 pg ml-1 on the control in subjects taking 200 mEq day-1 of sodium, and significant diuresis occurred when plasma concentration reached approximately 330.5 +/- 74.4 pg ml-1. alpha-hANP infusion caused a dose-dependent increase in cyclic GMP, no significant changes in plasma aldosterone and 18-hydroxycorticosterone, which were not influenced by indomethacin pretreatment. Plasma renin did not change in response to alpha-hANP infusion, which was significantly decreased (P less than 0.05) after indomethacin pretreatment. These results support that the renal effects of alpha-hANP may be exerted by prostaglandin-independent mechanisms. The renal effects occur at lower doses, and cardiovascular changes occur at higher doses of alpha-hANP.
在6名男性志愿者中，研究了静脉输注浓度为0.0125、0.025、0.05、0.1微克/千克·分钟的α-人心房利钠多肽（α-hANP）20分钟，在服用消炎痛（150毫克/天，每日3次，共3天）前后的肾脏、心血管和激素效应。在所有受试者中，观察到浓度在0.025至0.1微克/千克·分钟之间时出现剂量依赖性利尿和利钠作用，且不受消炎痛影响。在较高剂量（0.05微克/千克·分钟）的α-hANP作用下，舒张压显著降低（P<0.05），消炎痛预处理可减弱此作用。在摄入200毫当量/天钠的受试者中，对照时免疫反应性α-hANP的血浆浓度为73.7±25皮克/毫升，当血浆浓度达到约330.5±74.4皮克/毫升时出现显著利尿。α-hANP输注导致环磷酸鸟苷剂量依赖性增加，血浆醛固酮和18-羟皮质酮无显著变化，且不受消炎痛预处理影响。α-hANP输注后血浆肾素无变化，消炎痛预处理后血浆肾素显著降低（P<0.05）。这些结果支持α-hANP的肾脏效应可能通过不依赖前列腺素的机制发挥作用。α-hANP在较低剂量时产生肾脏效应，在较高剂量时产生心血管变化。
