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心房利钠肽生理水平对激素分泌的影响:对正常男性血管紧张素诱导的醛固酮分泌和肾素释放的抑制作用

Effect of physiological levels of atrial natriuretic peptide on hormone secretion: inhibition of angiotensin-induced aldosterone secretion and renin release in normal man.

作者信息

Cuneo R C, Espiner E A, Nicholls M G, Yandle T G, Livesey J H

机构信息

Department of Endocrinology, Princess Margaret Hospital, Christchurch, New Zealand.

出版信息

J Clin Endocrinol Metab. 1987 Oct;65(4):765-72. doi: 10.1210/jcem-65-4-765.

DOI:10.1210/jcem-65-4-765
PMID:2821056
Abstract

Large doses of atrial natriuretic peptide (ANP) inhibit renin and aldosterone secretion in normal man, but the effect of physiological levels is unknown. We, therefore, studied the effect of a low infusion rate of alpha-human ANP (alpha hANP; 0.5 microgram/min for 180 min) on the plasma corticosteroid response to graded physiological doses of angiotensin II (0.5, 1.0, 2.0, and 4.0 ng/kg X min, each for 30 min) and ACTH (6.25, 12.5, 25, and 50 mIU, each for 30 min) in six normal men eating a low salt diet (10 mmol sodium and 100 mmol potassium daily). The angiotensin II and ACTH infusions were given from 0900-1100 h on separate days, during which randomized infusions of placebo or alpha hANP were given from 0800-1100 h according to a single blind protocol. Plasma immunoreactive ANP levels were less than 10 pmol/L on the placebo day compared to 30-50 pmol/L during the alpha hANP infusions, and were not altered by either ACTH or angiotensin II. Compared with the control observations, there was no significant change in arterial pressure or heart rate during either the alpha hANP or angiotensin II infusions. ACTH infusions evoked an incremental response in plasma aldosterone and cortisol, and the dose-response relationship was unaltered by alpha hANP. In contrast, while an incremental and significant increase in plasma aldosterone in response to angiotensin II occurred with the placebo infusion, no significant increase occurred in response to angiotensin during the alpha hANP infusion. The slope of the angiotensin II/aldosterone regression line was significantly less during all alpha hANP infusions compared to that during the placebo infusion (P less than 0.02). In addition, on the ACTH infusion day significant suppression of both PRA (P less than 0.05) and plasma angiotensin II (P less than 0.008) occurred during the alpha hANP infusion compared to that during the placebo infusion, whereas PRA was equally suppressed by angiotensin II in the presence or absence of alpha hANP. alpha hANP also increased urine volume [176 +/- 31 (+/- SEM) vs. 113 +/- 19 mL/mmol creatinine with placebo; P less than 0.03] and sodium excretion (2.14 +/- 0.48 vs. 0.58 +/- 0.22 mmol/mmol creatinine with placebo; P less than 0.004) on the ACTH infusion days. With angiotensin II, urine volume was also significantly increased by alpha hANP (150 +/- 27 vs. 81 +/- 15 mL/mmol creatinine with placebo; P less than 0.03), and urine sodium excretion doubled.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

大剂量心房利钠肽(ANP)可抑制正常人的肾素和醛固酮分泌,但生理水平的心房利钠肽的作用尚不清楚。因此,我们研究了低输注速率的α-人ANP(αhANP;0.5微克/分钟,持续180分钟)对6名食用低盐饮食(每日10毫摩尔钠和100毫摩尔钾)的正常男性血浆皮质类固醇对分级生理剂量的血管紧张素II(0.5、1.0、2.0和4.0纳克/千克×分钟,各持续30分钟)和促肾上腺皮质激素(ACTH)(6.25、12.5、25和50毫国际单位,各持续30分钟)反应的影响。血管紧张素II和ACTH输注在不同日期的0900 - 1100时进行,在此期间,根据单盲方案在0800 - 1100时随机输注安慰剂或αhANP。安慰剂日血浆免疫反应性ANP水平低于10皮摩尔/升,而αhANP输注期间为30 - 50皮摩尔/升,且ACTH或血管紧张素II均未改变其水平。与对照观察相比,αhANP或血管紧张素II输注期间动脉压和心率均无显著变化。ACTH输注引起血浆醛固酮和皮质醇的递增反应,且剂量 - 反应关系未被αhANP改变。相反,安慰剂输注时血管紧张素II引起血浆醛固酮递增且显著增加,而αhANP输注期间血管紧张素II刺激未引起显著增加。与安慰剂输注期间相比,所有αhANP输注期间血管紧张素II /醛固酮回归线的斜率显著更小(P < 0.02)。此外,在ACTH输注日,与安慰剂输注相比,αhANP输注期间血浆肾素活性(P < 0.05)和血浆血管紧张素II(P < 0.008)均出现显著抑制,而血管紧张素II在有或无αhANP时对血浆肾素活性的抑制作用相同。在ACTH输注日,αhANP还增加了尿量[安慰剂组为113 ± 19毫升/毫摩尔肌酐,αhANP组为176 ± 31(±标准误);P < 0.03]和钠排泄(安慰剂组为0.58 ± 0.22毫摩尔/毫摩尔肌酐,αhANP组为2.14 ± 0.48;P < 0.004)。对于血管紧张素II,αhANP也显著增加了尿量(安慰剂组为81 ± 15毫升/毫摩尔肌酐,αhANP组为150 ± 27;P < 0.03),且尿钠排泄增加了一倍。(摘要截短至400字)

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