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AT1 and AT2 Mediated Renal Microvascular Actions: Lessons from Mice with Deletion of AT1 Receptors
Author(s) -
HarrisonBernard Lisa M,
Bivona Benjamin J,
Monjure Christopher J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a762-c
Subject(s) - angiotensin ii , angiotensin ii receptor type 1 , candesartan , endocrinology , medicine , receptor , vasodilation , angiotensin receptor , chemistry , biology
Angiotensin II (AngII) induced constriction of afferent (AA) and efferent (EA) arterioles of kidneys from wild type mice and AA of Ang type 1A receptor null (AT1A−/−) mice is inhibited by Ang type 1 receptor blockade (ARB; 4μM Candesartan). No evidence for an AngII/Ang type 2 receptor (AT2) mediated vasodilation was observed during ARB treatment. In the current study, we addressed the effects of ARB on AA and EA responses to AngII in mice lacking the Ang type 1B receptor (AT1B−/−). In order to determine if lifelong deletion of both AT1 receptor subtypes alters AT2 receptor mediated vasodilation, AngII responses of AA and EA were assessed in mice lacking both the AT1A and AT1B receptor subtypes (DKO). Experiments were conducted using the mouse in vitro blood perfused juxtamedullary nephron technique. Kidneys were harvested from AT1B−/− (n=18) and DKO (n=14) mice. Baseline AA and EA diameters averaged 13.5±0.7 (n=13) and 15.4±1.0μm (n=11) in AT1B−/− mice, and 18.6±1.1 (n=12) and 15.5±2.1μm (n=4) in DKO mice, respectively. Baseline AA diameters of DKO mice were significantly larger than AT1B−/−, while EA diameters were similar. 1 and 10nM AngII produced significant decreases in AA and EA diameters of AT1B−/− mice; AA decreased 10±2 and 25±4%, and EA decreased 11±4 and 32±6%, respectively. ARB did not alter baseline AA or EA diameters of AT1B−/− mice (P>0.05). 10nM AngII responses of AA and EA were blocked by ARB and averaged 95±5 (n=4) and 101±2% (n=4) of baseline, respectively. AA and EA of DKO mice did not respond to 100nM AngII and averaged 98±2 (n=12) and 100±2% (n=4) of baseline values. AA and EA of DKO mice did respond to 1μM NE with a significant decrease in diameter of 18±5 and 23±6%, respectively. In conclusion, our results do not support an effect of AT2 mediated vasodilation in afferent or efferent arterioles of WT, AT1A−/−, AT1B−/−, or DKO mice.