Wamberg Christian, Plovsing Ronni R, Sandgaard Niels C F, Bie Peter
Dept. of Physiology and Pharmacology, Institute of Medical Biology, 21 Winsløwparken, DK-5000 Odense, Denmark.
Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R971-80. doi: 10.1152/ajpregu.00262.2003. Epub 2003 Jul 17.
Evidence of biological activity of fragments of ANG II is accumulating. Fragments considered being inactive degradation products might mediate actions previously attributed to ANG II. The study aimed to determine whether angiotensin fragments exert biological activity when administered in amounts equimolar to physiological doses of ANG II. Cardiovascular, endocrine, and renal effects of ANG II, ANG III, ANG IV, and ANG-(1-7) (6 pmol.kg-1.min-1) were investigated in conscious dogs during acute inhibition of angiotensin I-converting enzyme (enalaprilate) and aldosterone (canrenoate). Furthermore, ANG III was investigated by step-up infusion (30 and 150 pmol.kg-1.min-1). Arterial plasma concentrations [ANG immunoreactivity (IR)] were determined by an ANG II antibody cross-reacting with ANG III and ANG IV. Metabolic clearance rates were higher for ANG III and ANG IV (391 +/- 19 and 274 +/- 13 ml.kg-1.min-1, respectively) than for ANG II (107 +/- 13 ml.kg-1.min-1). ANG II increased ANG IR by 60 +/- 7 pmol/ml, blood pressure by 30%, increased plasma aldosterone markedly (to 345 +/- 72 pg/ml), and plasma vasopressin transiently, while reducing glomerular filtration rate (40 +/- 2 to 33 +/- 2 ml/min), sodium excretion (50 +/- 7 to 16 +/- 4 micromol/min), and urine flow. Equimolar amounts of ANG III induced similar antinatriuresis (57 +/- 8 to 19 +/- 3 micromol/min) and aldosterone secretion (to 268 +/- 71 pg/ml) at much lower ANG IR increments ( approximately 1/7) without affecting blood pressure, vasopressin, or glomerular filtration rate. The effects of ANG III exhibited complex dose-response relations. ANG IV and ANG-(1-7) were ineffective. It is concluded that 1) plasma clearances of ANG III and ANG IV are higher than those of ANG II; 2) ANG III is more potent than ANG II in eliciting immediate sodium and potassium retention, as well as aldosterone secretion, particularly at low concentrations; and 3) the complexity of the ANG III dose-response relationships provides indirect evidence that several effector mechanisms are involved.
血管紧张素II（ANG II）片段具有生物活性的证据越来越多。一些曾被认为是无活性降解产物的片段，可能介导了先前归因于ANG II的作用。本研究旨在确定血管紧张素片段在以与生理剂量的ANG II等摩尔的量给药时是否发挥生物活性。在急性抑制血管紧张素I转换酶（依那普利拉）和醛固酮（坎利酸钾）期间，研究了ANG II、ANG III、ANG IV和ANG-(1-7)（6 pmol·kg-1·min-1）对清醒犬的心血管、内分泌和肾脏的影响。此外，通过逐步递增输注（30和150 pmol·kg-1·min-1）研究了ANG III。通过与ANG III和ANG IV交叉反应的ANG II抗体测定动脉血浆浓度[ANG免疫反应性（IR）]。ANG III和ANG IV的代谢清除率（分别为391±19和274±13 ml·kg-1·min-1）高于ANG II（107±13 ml·kg-1·min-1）。ANG II使ANG IR增加60±7 pmol/ml，血压升高30%，显著增加血浆醛固酮（至345±72 pg/ml），并使血浆血管加压素短暂升高，同时降低肾小球滤过率（从40±2降至33±2 ml/min）、钠排泄（从50±7降至16±4 μmol/min）和尿流。等摩尔量的ANG III在ANG IR升高幅度低得多（约为1/7）时诱导了类似的尿钠排泄减少（从57±8降至19±3 μmol/min）和醛固酮分泌（至268±71 pg/ml），且不影响血压、血管加压素或肾小球滤过率。ANG III的作用表现出复杂的剂量反应关系。ANG IV和ANG-(1-7)无效。研究得出以下结论：1）ANG III和ANG IV的血浆清除率高于ANG II；2）ANG III在引起即刻的钠和钾潴留以及醛固酮分泌方面比ANG II更有效，尤其是在低浓度时；3）ANG III剂量反应关系的复杂性间接证明涉及多种效应机制。
