Systemic effects of angiotensin III in conscious dogs during acute double blockade of the renin-angiotensin-aldosterone-system.
OBJECTIVE
The study was designed to determine (i) whether the effects of angiotensin III (AngIII) are similar to those of angiotensin II (AngII) at identical plasma concentrations and (ii) whether AngIII operates solely through AT1- receptors.


METHODS
Angiotensin II (3 pmol kg(-1) min(-1)-3.1 ng kg(-1) min(-1)) or AngIII (15 pmol kg(-1) min(-1)-14 ng kg(-1) min(-1)) was infused i.v. during acute inhibition of angiotensin converting enzyme (enalaprilate; 2 mg kg(-1)) and of aldosterone (canrenoate; 6 mg kg(-1) plus 1 mg kg(-1) h(-1)). Arterial plasma concentrations of angiotensins were determined by radioimmunoassay using a cross-reacting antibody to AngII. During ongoing peptide infusion, candesartan (2 mg kg(-1)) was administered to block the AT1-receptors.


RESULTS
Angiotensin immunoactivity in plasma increased to 60 +/- 10 pg mL(-1) during infusion of AngII or infusion of AngIII. AngII significantly increased mean arterial blood pressure (+14 +/- 4 mmHg) and plasma aldosterone by 79% (+149 +/- 17 pg mL(-1)) and reduced plasma renin activity and sodium excretion (-41 +/- 16 mIU L(-1) and -46 +/- 6 micromol min(-1) respectively). AngIII mimicked these effects and the magnitude of AngIII responses was statistically indistinguishable from those of AngII. All measured effects of both peptides were blocked by candesartan.


CONCLUSIONS
At the present arterial plasma concentrations, AngIII is equipotent to AngII with regard to effects on blood pressure, aldosterone secretion and renal functions, and these AngIII effects are mediated through AT1- receptors. The metabolic clearance rate of AngIII is five times that of AngII.
Gammelgaard
I
I
Department of Physiology and Pharmacology, Institute of Medical Biology, University of Southern Denmark, Odense, Denmark.
Wamberg
S
S
Bie
P
P
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000805:Angiotensin III / Q000097:blood / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D008657:Metabolic Clearance Rate; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; D000805:Angiotensin III; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin; D015773:Enalaprilat; C081643:candesartan