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Inhibition of the Janus (JAK)/Signal Transducers of Activated Transcription (STAT) Pathway prevents the Development of Angiotensin II‐induced Hypertension
Author(s) -
BanesBerceli Amy K.L.,
Brands Michael W,
Labazi Hicham,
Springfield Vanessa
Publication year - 2008
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.22.1_supplement.969.33
Subject(s) - angiotensin ii , medicine , jak stat signaling pathway , stat , endocrinology , renin–angiotensin system , in vivo , blood pressure , western blot , janus kinase , stat protein , chemistry , signal transduction , stat3 , receptor , biology , gene , biochemistry , microbiology and biotechnology , tyrosine kinase
Angiotensin II (ANG II) is a major physiologic and pathophysiologic controller of arterial pressure, but the molecular mechanisms underlying that effect are not completely understood. ANG II activates the JAK/STAT pathway in vitro and in vivo in models of type I diabetes but whether this activation occurs in hypertension and is required for ANG II‐mediated increases in blood pressure are unknown. Therefore we tested the hypothesis that inhibition of the JAK/STAT pathway would attenuate ANG II‐induced hypertension. We utilized male Sprague‐Dawley rats, chronically catheterized for 24 hr/day iv infusion and mean arterial pressure (MAP) measurements. All rats were maintained on a high‐salt intake (~12 mEq/day), and after control measurements ANG II (10 ng/kg/min, iv ) was infused with or without the JAK2 inhibitor AG490 (10 ng/kg/min, iv ). After 5 days of ANG II infusion the rats receiving AG490 had significantly lower MAP than the ANG II alone rats (106 + 6.1 vs 144 + 4.9 mm Hg, respectively). When AG490 was stopped during continued ANG II infusion, MAP rose within 1 day to match MAP in the ANG II alone group (158+ 2.1 vs 168 + 6.9, respectively). Western blot analysis revealed that JAK2 activation was significantly inhibited in the ANG II/AG490‐treated rats. From these data we conclude that activation of the JAK/STAT pathway is critical for the development of ANG II‐induced hypertension. (AHA SDG ABB, HL‐56259, HL‐74167 MWB).