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Diverse impairment of vasodilator pathways in brain following selective interference with PPAR‐gamma in vascular muscle
Author(s) -
Modrick Mary L.,
Chrissobolis Sophocles,
Halabi Carmen M.,
Sigmund Curt D.,
Faraci Frank M.
Publication year - 2009
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.23.1_supplement.613.17
Subject(s) - medicine , endocrinology , peroxisome proliferator activated receptor gamma , vasodilation , vascular smooth muscle , basilar artery , cerebral circulation , cerebral arteries , chemistry , biology , peroxisome proliferator activated receptor , receptor , smooth muscle
Peroxisome proliferator‐activated receptor‐gamma (PPARg) may play an important protective role in the vasculature. We examined the hypothesis that selective interference with PPARg in vascular muscle would alter regulation of vasomotor tone. We studied basilar arteries from mice expressing a dominant negative mutation in human PPARg (P467L) under the control of the smooth muscle myosin heavy chain promoter (S‐P467L). We examined responses to stimuli that produce vasodilation via nitric oxide and cGMP (acetylcholine, ACh; nitroprusside, NP), cAMP (forskolin), and potassium channels [cromakalim and potassium ion (K+)]. In non‐transgenic controls, all agonists produced dilation of the basilar artery in vitro. In S‐P467L mice, responses to ACh, NP, forskolin, and activators of K+ channels were reduced by 40‐70% compared to controls (P<0.05). For example, vasodilation to K+ (10 mM) was 67±6 and 22±4% in control (n=9) and S‐P467L (n=6) mice, respectively (P<0.01). Arteries from both groups responded similarly to the calcium channel agonist Bay K8644 and the calcium channel antagonist nifedipine. These data provide the first evidence that cell‐specific interference with the function of PPARg in vascular muscle produces marked, but selective, impairment of diverse vasodilator pathways. Thus, normal PPARg function in vascular muscle plays an essential role in regulation of cerebral vascular tone.