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 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.
|Keywords||AT1a receptors, Angiotensin IV, Blood pressure, Cortical blood flow, Insulin-regulated aminopeptidase, Knockout mice, aminopeptidase, angiotensin 1 receptor, angiotensin 1A receptor, angiotensin 1B receptor, angiotensin 2 receptor, angiotensin II, angiotensin II [3-8], animal experiment, article, blood pressure, candesartan, catheter, controlled study, dose response, endothelin 1, femur, kidney blood flow, kidney cortex, kidney tubule pressure, kidney vascular resistance, knockout mouse, laser Doppler flowmetry, low drug dose, male, mean arterial pressure, mouse, nonhuman, pressor response, priority journal, vasoconstriction, wild type|
|Persistent URL||dx.doi.org/10.1097/HJH.0b013e3283343250, hdl.handle.net/1765/18686|
|Journal||Journal of Hypertension|
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