TY - JOUR
T1 - Renal vasoconstrictor and pressor responses to angiotensin IV in mice are AT1a-receptor mediated
AU - Yang, Rui
AU - Walther, Thomas
AU - Gembardt, Florian
AU - Smolders, Ilse
AU - Vanderheyden, Patrick
AU - Albiston, Anthony
AU - Chai, Siew
AU - Dupont, Alain
PY - 2010
Y1 - 2010
N2 - 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 AT1a, 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.
AB - 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 AT1a, 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.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19907343
U2 - 10.1097/HJH.0b013e3283343250
DO - 10.1097/HJH.0b013e3283343250
M3 - Article
SN - 0263-6352
VL - 28
SP - 487
EP - 494
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 3
ER -