BACKGROUND AND PURPOSE: Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-activated transcription factor expressed in vascular cells, is protective of the vasculature. We hypothesized that activation of PPARgamma could prevent hypertensive remodeling of cerebral arteries and improve vascular function. METHODS: Ten female Sprague-Dawley rats were treated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) for 5 weeks, 8 were treated with l-NAME plus the PPARgamma activator rosiglitazone, and 8 received no treatment and served as controls. Blood pressure, myogenic activity, passive diameters and wall thickness of cerebral arteries, and brain capillary density were compared between the groups. RESULTS: Treatment with l-NAME caused an increase in arterial blood pressure that was sustained with rosiglitazone treatment. l-NAME also caused inward hypertrophic remodeling and enhanced myogenic reactivity of cerebral arteries that was reversed by rosiglitazone. In addition, l-NAME hypertension caused rarefaction of brain capillaries by approximately 12%, whereas treatment with rosiglitazone increased capillary density by approximately 20%. CONCLUSIONS: PPARgamma activation may be an effective and clinically relevant way to prevent hypertensive remodeling of cerebral arteries and capillary rarefaction as well as improving vascular function without affecting blood pressure.
BACKGROUND AND PURPOSE: Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-activated transcription factor expressed in vascular cells, is protective of the vasculature. We hypothesized that activation of PPARgamma could prevent hypertensive remodeling of cerebral arteries and improve vascular function. METHODS: Ten female Sprague-Dawley rats were treated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) for 5 weeks, 8 were treated with l-NAME plus the PPARgamma activator rosiglitazone, and 8 received no treatment and served as controls. Blood pressure, myogenic activity, passive diameters and wall thickness of cerebral arteries, and brain capillary density were compared between the groups. RESULTS: Treatment with l-NAME caused an increase in arterial blood pressure that was sustained with rosiglitazone treatment. l-NAME also caused inward hypertrophic remodeling and enhanced myogenic reactivity of cerebral arteries that was reversed by rosiglitazone. In addition, l-NAMEhypertension caused rarefaction of brain capillaries by approximately 12%, whereas treatment with rosiglitazone increased capillary density by approximately 20%. CONCLUSIONS:PPARgamma activation may be an effective and clinically relevant way to prevent hypertensive remodeling of cerebral arteries and capillary rarefaction as well as improving vascular function without affecting blood pressure.
Authors: Federico Biscetti; Eleonora Gaetani; Andrea Flex; Tamar Aprahamian; Teresa Hopkins; Giuseppe Straface; Giovanni Pecorini; Egidio Stigliano; Roy C Smith; Flavia Angelini; John J Castellot; Roberto Pola Journal: Diabetes Date: 2008-02-11 Impact factor: 9.461
Authors: T Michael De Silva; Mary L Modrick; Pimonrat Ketsawatsomkron; Cynthia Lynch; Yi Chu; Christopher J Pelham; Curt D Sigmund; Frank M Faraci Journal: Hypertension Date: 2014-09-02 Impact factor: 10.190
Authors: T Michael De Silva; Pimonrat Ketsawatsomkron; Christopher Pelham; Curt D Sigmund; Frank M Faraci Journal: Hypertension Date: 2014-11-10 Impact factor: 10.190
Authors: Mary L Modrick; Dale A Kinzenbaw; Yi Chu; Curt D Sigmund; Frank M Faraci Journal: Am J Physiol Regul Integr Comp Physiol Date: 2012-03-28 Impact factor: 3.619
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