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Chlothalidone inhibits angiotensin‐induced apoptosis in vascular smooth muscle
Author(s) -
Woodman Ryan,
Van Aken Julie,
Lockette Warren
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.20.5.a1177-b
Subject(s) - vascular smooth muscle , chlorthalidone , apoptosis , angiotensin ii , receptor , caspase , medicine , endocrinology , chemistry , caspase 3 , microbiology and biotechnology , biology , programmed cell death , biochemistry , diuretic , smooth muscle
Angiotensin II (Ang II) stops progression of the vascular smooth muscle cell (VSMC) cycle in the G/S1 phase, and the action of this ligand on the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R) induces vascular hypertrophy, or apoptosis, respectively. We tested our hypothesis that chlorthalidone may mediate its salutary effect not only by lowering blood pressure, but also by inhibiting Ang II‐induced apoptosis. Both A10 and A7r5 lines of cultured VSMCs, derived from embryonic rat thoracic aortae, express the AT1R and AT2R. We treated confluent cultures of these lines with 1 uM Ang II in the presence or absence of 30 uM chlorthalidone and measured apoptosis at 4 h and 24 h. Apoptosis was determined by quantifying the activity of the caspase‐3 enzyme released into the culture medium. Caspase‐3 was measured by following the luminescence generated by the caspase‐dependent cleavage of DEVD‐aminoluciferin. Chlorthalidone significantly inhibited Ang II‐induced apoptosis in VSMC at 4 h and 24 h. Values are expressed in luminescence units ± SEM, *denotes p < 0.01 compared to culture media alone.Chlorthalidone significantly inhibited angiotensin II‐induced efflux of caspase‐3 from confluent, cultured VSMCs. The effects of this diuretic were not due to direct inhibition of caspase activity, as chlorthalidone had no direct effect on the enzymatic cleavage of the substrate in a range of 30 to 1000 units of caspase‐3 activity. Chlorthalidone may prove salutary in preventing programmed cell death in aging vascular smooth muscle.