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Am J Physiol Regul Integr Comp Physiol (July 17, 2003). doi:10.1152/ajpregu.00262.2003
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Submitted on May 12, 2003
Accepted on July 7, 2003

Effects of different angiotensins during acute, double blockade of the renin system in conscious dogs

Christian Wamberg1, Ronni R Plovsing1, Niels C F Sandgaard1, and Peter Bie1*

1 Department of Physiology and Pharmacology, Institute of Medical Biology, University of Southern Denmark, Odense, DK-5000, Denmark

* To whom correspondence should be addressed. E-mail: pbie{at}health.sdu.dk.

Evidence of biological activity of fragments of angiotensin II (AngII) is accumulating. Fragments considered being inactive degradation products might mediate actions previously attributed to AngII. The study aimed to determine whether angiotensin fragments exert biological activity when adminis-tered in amounts equimolar to physiological doses of AngII. Cardiovascular, endocrine, and renal effects of AngII, AngIII, AngIV, and Ang(1-7) (6 pmol/kg/min) were investigated in conscious dogs during acute inhibition of ACE (enalaprilate) and aldosterone (canrenoate). Further, AngIII was in-vestigated by step-up infusion (30 and 150 pmol/kg/min). Arterial plasma concentrations (AngIR) were determined by an AngII antibody cross-reacting with AngIII and AngIV. Metabolic clearance rates were higher for AngIII and AngIV (391±19 and 274±13 ml/kg/min, respectively) than for AngII (107±13 ml/kg/min). AngII increased AngIR 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 µmol/min) and urine flow. Equimolar amounts of AngIII induced similar antinatriuresis (57±8 to 19±3 µmol/min) and aldosterone secretion (to 268±71 pg/ml) at much lower AngIR increments (about 1/7) without affecting blood pressure, vasopressin, or GFR. The effects of AngIII exhibited complex dose-response relations. AngIV and Ang(1-7) were ineffective. It is concluded that (i) plasma clearances of AngIII and AngIV are higher than AngII, (ii) AngIII is more potent than AngII in eliciting immediate sodium and potassium retention as well as aldosterone secretion particularly at low concentrations, and (iii) the complexity of the AngIII dose-response relationships provides indirect evidence that sev-eral effector mechanisms are involved.




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