Premium
Deoxycorticosterone acetate (DOCA)‐salt exacerbates hypertension and vascular dysfunction in mice expressing dominant negative Peroxisome Proliferator‐Activated Receptor‐gamma (PPARG) in smooth muscle
Author(s) -
Ketsawatsomkron Pimonrat,
Davis Deborah R,
Grobe Justin L,
Sigmund Curt D
Publication year - 2013
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.27.1_supplement.708.10
Subject(s) - medicine , myograph , endocrinology , peroxisome proliferator activated receptor gamma , blood pressure , endothelin receptor , mesenteric arteries , receptor , chemistry , peroxisome proliferator activated receptor , artery
PPARG, a ligand‐activated transcription factor plays a critical role in regulation of blood pressure and vascular function. We hypothesized that smooth muscle PPARG protects against hypertension and resistance vessel dysfunction. Mice expressing dominant negative PPARG (S‐P467L) in smooth muscle or non‐transgenic control (NT) were implanted with DOCA‐salt and allowed ad lib. 0.15 M NaCl for 21 days in addition to chow and tap water. Blood pressure was monitored by telemetry and mesenteric arterial function was assessed by pressurized myograph. At baseline, 24‐hour mean arterial pressure (MAP) was similar between NT and S‐P467L mice, while the transgenic mice were tachycardic. DOCA‐salt increased MAP in all animals, but S‐P467L mice exhibited increased sensitivity (Δ mmHg; S‐P467L n=5, +34.2±7.3 p=0.003 vs baseline; NT n=3, +15.0±8.5 p=0.152 vs baseline). Heart rate was similarly decreased in both groups after DOCA‐salt. Vasorelaxation to acetylcholine was impaired in S‐P467L mesenteric arteries compared to NT at baseline and this effect was further exaggerated after DOCA salt. Vasopressin‐induced constriction was significantly reduced in S‐P467L compared to NT arteries after DOCA‐salt, but the response to KCl and endothelin‐1 did not differ between groups. We conclude that impaired smooth muscle PPARG sensitizes the effects of DOCA‐salt induced hypertension and vascular dysfunction.