Systemic effects of angiotensin III in conscious dogs during acute double blockade of the renin-angiotensin-aldosterone-system.
Aims: 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 AT(1)- 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 AT(1)-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 mumol 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. Conclusion: 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 AT(1)- receptors. The metabolic clearance rate of AngIII is five times that of AngII.[1]References
- Systemic effects of angiotensin III in conscious dogs during acute double blockade of the renin-angiotensin-aldosterone-system. Gammelgaard, I., Wamberg, S., Bie, P. Acta physiologica (Oxford, England) (2006) [Pubmed]
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