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1 Dept. of Physiology & Pharmacology, Institute of Medical Biology, University of Southern Denmark, Odense, DK-5000, Denmark
2 Dept. of Nuclear Medicine, Odense University Hospital, Odense, DK-5000, Denmark
3 Dept. of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, DK-2200, Denmark
* To whom correspondence should be addressed. E-mail: pbie{at}health.sdu.dk.
Angiotensin peptides different from angiotensin II (AngII) exhibit biological activities, possibly mediated by receptors distinct from the AT1 and AT2 receptors. This study was designed to investigate the effects of AngIII, Ang-(1-7) and AngIV, in doses equimolar to physiological amounts of AngII. Six men were studied after 4 days of low-sodium diet (30 mmol/day). In each subject, five separate investigations were performed after acute pretreatment with canrenoate and captopril to inhibit aldosterone actions and AngII synthesis, respectively. Peptides were infused at 3 pmol/kg/min for 180 min. AngII infusion increased plasma angiotensin immunoreactivity (AngIR) to 53±6 pg/ml (+490%), plasma aldosterone to 342±38 pg/ml (+109%) and blood pressure by 27%. Glomerular filtration rate (GFR) decreased by 16%. Concomitantly, clearance of endogenous lithium fell by 66%, and fractional reabsorption of sodium in the proximal tubule increased from 77 to 92% while absolute proximal reabsorption remained constant. AngII decreased sodium excretion by 70%, potassium excretion by 50%, and urine flow by 80%, while urine osmolality increased. AngIII also increased plasma aldosterone markedly (+45%), however, without changing AngIR, GFR or renal excretion of water or salt. In the time control studies, plasma renin activity (PRA) decreased markedly (~700 mIU/L to ~200 mIU/L). AngII enhanced this decrease, while the other peptides did not affect it. Ang-(1-7) and AngIV did not elicit persisting changes. It is concluded that (i) plasma clearances of AngIII and AngIV are substantially higher than that of AngII (but undeterminable in the present setting) (ii) a mildly hypertensive dose of AngII causes hypofiltration, urinary concentration, and sodium and potassium retention in the absence of changes in vasopressin and atrial natriuretic peptide, and (iii) AngIII may increase aldosterone secretion by very small increases in plasma peptide concentrations unmeasurable by usual radioimmunoassay techniques.
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