Carey R M, Vaughan E D, Peach M J, Ayers C R
J Clin Invest. 1978 Jan;61(1):20-31. doi: 10.1172/JCI108919.
This study was designed to compare the effect of [des-Aspartyl(1)]-angiotensin II ([des-Asp]-A II) and angiotensin II (A II) on blood pressure and aldosterone production in man under conditions of normal and low sodium (Na) intake. Seven normal male subjects in balance on constant normal Na intake (U(Na) V 160.3+/-5.0 meq/24 h) for 5 days received A II and [des-Asp]-A II infusions on two consecutive days; 1 mo later they were restudied after 5 days of low Na intake (U(Na) V 10.5+/-1.6 meq/24 h). Each dose was infused for 30 min, sequentially. During normal Na intake, [des-Asp]-A II from 2 to 18 pmol/kg per min increased mean blood pressure from 85.2+/-3 to 95.3+/-5 mm Hg and plasma aldosterone concentration from 5.2+/-1.1 to 14.3+/-1.9 ng/100 ml. During low Na intake, the same dose of [des-Asp]-A II increased mean blood pressure from 83.7+/-3 to 86.7+/-3 mm Hg and plasma aldosterone concentration from 34.4+/-6.0 to 51.0+/-8.2 ng/100 ml. In contrast, A II from 2 to 6 pmol/kg per min during normal Na intake increased mean blood pressure from 83.3+/-4 to 102.3+/-4 mm Hg and plasma aldosterone concentration from 7.0+/-2.2 to 26.8+/-2.0 ng/100 ml; during low Na intake, A II increased mean blood pressure from 83.0+/-3 to 96.0+/-4 mm Hg and plasma aldosterone concentration from 42.0+/-9.7 to 102.2+/-15.4 ng/100 ml. A II and [des-Asp]-A II were equally effective in suppressing renin release. Plasma cortisol and Na and K concentration did not change. The effects of two doses (2 and 6 pmol/kg per min) of each peptide on blood pressure and aldosterone production were evaluated. During normal Na intake, [des-Asp]-A II had 11-36% of the pressor activity and 15-30% of the steroidogenic activity of A II. Na deprivation attenuated the pressor response and sensitized the adrenal cortex to both peptides, but the increase in steroidogenesis was greater with [des-Asp]-A II than with A II. The dose-response curves for [des-Asp]-A II with respect to blood pressure and aldosterone production were not parallel, and although no maximum was established for A II, [des-Asp]-A II was less efficacious.In summary, (a) [des-Asp]-A II has biologic activity in man, (b) [des-Asp]-A II is less efficacious than A II in stimulating aldosterone production, (c) Na deprivation sensitizes the adrenal cortex more markedly to [des-Asp]-A II than A II, and (d) dose-response curves for the two peptides differ, suggesting the possibility that they act at different receptor sites in vascular smooth muscle and the adrenal cortex.
本研究旨在比较[去天冬氨酸(1)]-血管紧张素II([去天冬氨酸]-A II)与血管紧张素II(A II)在正常钠(Na)摄入和低钠摄入条件下对人体血压及醛固酮分泌的影响。7名正常男性受试者在5天内保持恒定正常钠摄入量(尿钠排泄量(U(Na))为160.3±5.0 meq/24 h)，并在连续两天接受A II和[去天冬氨酸]-A II静脉输注；1个月后，在低钠摄入5天(尿钠排泄量(U(Na))为10.5±1.6 meq/24 h)后再次进行研究。每种剂量均按顺序输注30分钟。在正常钠摄入期间，[去天冬氨酸]-A II剂量从2至18 pmol/kg每分钟可使平均血压从85.2±3 mmHg升高至95.3±5 mmHg，血浆醛固酮浓度从5.2±1.1 ng/100 ml升高至14.3±1.9 ng/100 ml。在低钠摄入期间，相同剂量的[去天冬氨酸]-A II可使平均血压从83.7±3 mmHg升高至86.7±3 mmHg，血浆醛固酮浓度从34.4±6.0 ng/100 ml升高至51.0±8.2 ng/100 ml。相比之下，在正常钠摄入期间，A II剂量从2至6 pmol/kg每分钟可使平均血压从83.3±4 mmHg升高至102.3±4 mmHg，血浆醛固酮浓度从7.0±2.2 ng/100 ml升高至26.8±2.0 ng/100 ml；在低钠摄入期间，A II可使平均血压从83.0±3 mmHg升高至96.0±4 mmHg，血浆醛固酮浓度从42.0±9.7 ng/100 ml升高至102.2±15.4 ng/ ml。A II和[去天冬氨酸]-A II在抑制肾素释放方面同样有效。血浆皮质醇、钠和钾浓度未发生变化。评估了每种肽的两种剂量(2和6 pmol/kg每分钟)对血压和醛固酮分泌的影响。在正常钠摄入期间，[去天冬氨酸]-A II的升压活性为A II的11 - 36%，类固醇生成活性为A II的15 - 30%。钠缺乏减弱了升压反应，并使肾上腺皮质对两种肽更敏感，但[去天冬氨酸]-A II引起的类固醇生成增加幅度大于A II。[去天冬氨酸]-A II关于血压和醛固酮分泌的剂量反应曲线不平行，并且尽管未确定A II的最大效应，但[去天冬氨酸]-A II的效力较低。总之，(a)[去天冬氨酸]-A II在人体具有生物活性，(b)[去天冬氨酸]-A II在刺激醛固酮分泌方面比A II效力低，(c)钠缺乏使肾上腺皮质对[去天冬氨酸]-A II比对A II更明显地敏感，(d)两种肽的剂量反应曲线不同，提示它们可能在血管平滑肌和肾上腺皮质中的不同受体位点起作用。
