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Importance of the chemokine RANTES in the development of angiotensin II‐induced hypertension and vascular dysfunction
Author(s) -
Budzyn Klaudia,
Lob Heinrich E,
McCann Louise A,
Goronzy Jorg J,
Weyand Cornelia M,
Harrison David G,
Guzik Tomasz J
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.1210.8
Subject(s) - angiotensin ii , chemokine , medicine , endocrinology , endothelial dysfunction , renin–angiotensin system , endothelium , inflammation , blood pressure
Recent studies in our laboratory have revealed a major role for the T cell in the development of angiotensin II‐induced hypertension and associated vascular dysfunction, in parallel with increased levels of the chemokine, RANTES, in blood vessels. These observations suggest an important role for RANTES in stimulating T cell migration during the development of angiotensin II‐induced hypertension. Hence, we have sought to determine the role of RANTES in the development of hypertension and vascular dysfunction induced by angiotensin II. C57Bl/6 and RANTES −/− mice were infused with angiotensin II (490 ng/min/kg) for 14 days, with the hypertensive response to angiotensin II being markedly blunted in RANTES −/− relative to C57Bl/6 mice ( P <0.05). Moreover, whilst angiotensin II infusion caused severe impairment of endothelium‐dependent relaxation in isolated aortic segments from C57Bl/6 mice, it had no such effect on relaxation responses of segments from RANTES −/− mice. This preserved endothelial function occurred in parallel with lower superoxide production in these vessels relative to those from C57Bl/6 mice ( P <0.05), as well as reduced T cell infiltration. These observations demonstrate that RANTES contributes significantly to the hypertensive response and vascular dysfunction induced by angiotensin II. Thus, selective suppression of RANTES might represent a novel strategy for the treatment of the vascular complications associated with the development of hypertension.