Effects of angiotensin-(1-7) and other bioactive components of the renin–angiotensin system on vascular resistance and noradrenaline release in rat kidney

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Abstract
Objective Angiotensin (Ang) is broken down enzymatically to several different metabolites which, in addition to Ang II, may have important biological effects in the kidney. This study investigates the role of Ang metabolites on vascular resistance and noradrenaline release in the rat kidney. Methods and results In rat isolated kidney Ang I, Ang II, Ang III, Ang IV and des-Asp-Ang I induced pressor responses and enhanced noradrenaline release to renal nerve stimulation (RNS) in an concentration-dependent manner, with the following rank order of potency (EC50): Ang II ≥ Ang III > Ang I = des-Asp-Ang I > Ang IV. All effects were blocked by the AT1-receptor antagonist EXP 3174 (0.1 μmol/l) but not by the AT2-receptor antagonist PD 123319 (1 μmol/l). Angiotensin-converting enzyme (ACE) inhibition by captopril (10 μmol/l) abolished the effect of Ang I and des-Asp-Ang I but had no influence on the effect of the other metabolites. Ang-(1-7) blocked the effects of Ang I and Ang II, being 10 times more potent against Ang I than Ang II. The selective Ang-(1-7) receptor blocker d-Ala7-Ang-(1-7) (10 μmol/l) did not influence the inhibitory effects of Ang-(1-7). Ang-(1-7) (10 μmol/l) by itself had no influence on vascular resistance and RNS-induced noradrenaline release. Conclusion Ang I, Ang II, Ang III, Ang IV and des-Asp-Ang I regulate renal vascular resistance and noradrenaline release by activation of AT1 receptors. In the case of Ang I and des-Asp-Ang I this depends on conversion by ACE. Ang-(1-7) may act as a potent endogenous inhibitor/antagonist of ACE and the AT1-receptors, respectively.