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 (EC(50)): Ang II >or= Ang III > Ang I = des-Asp-Ang I > Ang IV. All effects were blocked by the AT(1)-receptor antagonist EXP 3174 (0.1 micromol/l) but not by the AT(2)-receptor antagonist PD 123319 (1 micromol/l). Angiotensin-converting enzyme (ACE) inhibition by captopril (10 micromol/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 micromol/l) did not influence the inhibitory effects of Ang-(1-7). Ang-(1-7) (10 micromol/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 AT(1) 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 AT(1)-receptors, respectively.
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 (EC(50)): Ang II >or= Ang III > Ang I = des-Asp-Ang I > Ang IV. All effects were blocked by the AT(1)-receptor antagonist EXP 3174 (0.1 micromol/l) but not by the AT(2)-receptor antagonist PD 123319 (1 micromol/l). Angiotensin-converting enzyme (ACE) inhibition by captopril (10 micromol/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 micromol/l) did not influence the inhibitory effects of Ang-(1-7). Ang-(1-7) (10 micromol/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 AT(1) 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 AT(1)-receptors, respectively.
Authors: Liliya M Yamaleyeva; Sarah H Lindsey; Jasmina Varagic; Li Li Zhang; Patricia E Gallagher; Alex F Chen; Mark C Chappell Journal: J Cardiovasc Pharmacol Date: 2012-06 Impact factor: 3.105
Authors: Jianli Bi; Stephen A Contag; Luke C Carey; Lijun Tang; Nancy K Valego; Mark C Chappell; James C Rose Journal: J Renin Angiotensin Aldosterone Syst Date: 2012-11-16 Impact factor: 1.636
Authors: Marta Kuczeriszka; Elzbieta Kompanowska-Jezierska; Janusz Sadowski; Minolfa C Prieto; L Gabriel Navar Journal: Am J Hypertens Date: 2018-03-10 Impact factor: 2.689
Authors: J Stegbauer; S A Potthoff; I Quack; E Mergia; T Clasen; S Friedrich; O Vonend; M Woznowski; E Königshausen; L Sellin; L C Rump Journal: Br J Pharmacol Date: 2011-07 Impact factor: 8.739
Authors: Henning Hoch; Johannes Stegbauer; Sebastian A Potthoff; Lutz Hein; Ivo Quack; Lars Christian Rump; Oliver Vonend Journal: Br J Pharmacol Date: 2011-05 Impact factor: 8.739
Authors: Lydia Hering; Masudur Rahman; Henning Hoch; Lajos Markó; Guang Yang; Annika Reil; Mina Yakoub; Vikram Gupta; Sebastian A Potthoff; Oliver Vonend; Donna L Ralph; Susan B Gurley; Alicia A McDonough; Lars C Rump; Johannes Stegbauer Journal: J Am Soc Nephrol Date: 2020-02-21 Impact factor: 10.121