Objectives: Angiotensin (Ang) IV was reported to induce renal vasoconstriction or vasodilation in rats via AT1 or AT4 receptors, respectively, whereby the latter one has been identified to be the insulin-regulated aminopeptidase (IRAP). We investigated the effects of Ang IV on mean arterial pressure (MAP) and renal cortical blood flow (CBF) in AT 1a, AT1b, AT2 receptor and IRAP knockout (-/-) mice and their corresponding wild-type littermates. Ang II, known as a renal vasoconstrictor in mice, was used as a reference. Methods: MAP was recorded via a femoral catheter and CBF was measured using a light amplification by stimulated emission of radiation (LASER) Doppler probe; cortical vascular resistance (CVR) was calculated as MAP divided by CBF. Results: Baseline MAP, CBF and CVR in AT1a (-/-) mice were significantly lower than wild-type mice. AT2 (-/-) mice had a significantly higher baseline MAP, but similar CBF. In wild-type mice, Ang IV and Ang II induced dose-dependent pressor and renal vasoconstrictor responses, which were antagonized by the AT1 receptor blocker candesartan. These responses were almost completely absent in AT1a (-/-) mice, but were enhanced in AT2 (-/-) mice; responses in AT1b (-/-) and IRAP (-/-) mice were comparable to those in corresponding wild-type mice. Conclusion: Ang IV mediates pressure and renal vasoconstrictor effects in mice via AT1a receptors, whereas IRAP/AT4 is not involved.

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doi.org/10.1097/HJH.0b013e3283343250, hdl.handle.net/1765/18686
Journal of Hypertension
Erasmus MC: University Medical Center Rotterdam

Yang, R, Walther, T, Gembardt, F, Smolders, I, Vanderheyden, P, Albiston, A.L, … Dupont, A.G. (2010). Renal vasoconstrictor and pressor responses to angiotensin IV in mice are AT1a-receptor mediated. Journal of Hypertension, 28(3), 487–494. doi:10.1097/HJH.0b013e3283343250