Background & Objective: 

Recently a new derivative of angiotensin II (Ang II, the major bioactive peptide of the renin-angiotensin system) called angiotensin A (Ang A), was identified in human plasma, and was shown to be increased in end stage renal failure (Vera Jankowski et al. 2007). Similar to Ang II, Ang A stimulates both AT1 and AT2 receptors, although with higher affinity for AT2 receptors. The objective of the study was to investigate the blood pressure (mean blood pressure, MAP) and renal hemodynamic response (renal blood flow, RBF) to Ang A as compared with Ang II in normal adult rats and the involvement of AT1 and/or AT2 receptors in these responses. Binding properties of Ang A/II in CHO cells recombinantly expressing human AT1 receptors were also studied.

Methods and results: 

I.v. bolus injections of Ang A/II (0.01, 0.1, 1, 10 nmol/kg) dose-dependently increased MAP and decreased RBF. These effects were abolished by AT1 receptor blockade with candesartan (1 mg/kg), but were not altered by AT2 receptor blockade with PD 123315 (1 mg/kg). Intrarenal (i.r.) infusion of Ang A/II (1, 10, 100, 1000 pmol/20 ml/min) dose-dependently reduced RBF and increased MAP; these effects were blocked by candesartan (5 mg/kg, i.r.) but not affected by PD 123315 (0.5 mg/kg, i.r. bolus + 0.3 mg/h/kg, i.r. infusion). Administration of selective AT2 receptor agonists via i.v. bolus injection (CGP42112, 10 mg/kg or compound 21, 300 ng/kg) and i.r. infusion (compound 21, 1 or 10 ng/kg) did not alter MAP or RBF. Ang A was about 10 times less potent than Ang II in both i.v. bolus and i.r. infusion studies. In vitro [125I]-sar1-ile8-angiotensin binding experiments indicated that Ang A has the same nanomolar affinity for AT1 receptor compared to Ang II.

Conclusions: 

Ang A, a recently detected naturally occurring peptide, increases MAP and induces renal vasoconstriction via stimulation of AT1 receptors but is less potent than Ang II. We could not detect any AT2 receptor-mediated effect of Ang A/II on blood pressure and RBF possibly due to the low expression of these receptors in normal adult animals.