Renal vasoconstrictor and pressor responses to angiotensin IV in mice are AT1a-receptor mediated

Objectives Angiotensin (Ang) IV was reported to induce renal vasoconstriction or vasodilation in rats via AT(1) or AT(4) 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), AT(1b), AT(2) 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 AT(1a) (-/-) mice were significantly lower than wild-type mice. AT(2) (-/-) 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 AT(1) receptor blocker candesartan. These responses were almost completely absent in AT(1a) (-/-) mice, but were enhanced in AT(2) (-/-) mice; responses in AT(1b) (-/-) and IRAP (-/-) mice were comparable to those in corresponding wild-type mice. Conclusion Ang IV mediates pressure and renal vasoconstrictor effects in mice via AT(1a) receptors, whereas IRAP/AT(4) is not involved. J Hypertens 28:487-494 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.