Dominant‐negative mutation of endothelial peroxisome proliferator‐activated receptor γ (PPAR‐γ) impairs spontaneous baroreflex gain in mice

In rats with diet‐induced obesity (DIO), low baroreflex gain (BRG) is restored by treatment with rosiglitazone (ROSI), a PPAR‐γ agonist, but the mechanism is unknown. DIO impairs brain baroreflex pathways, yet ROSI does not cross the endothelial blood‐brain barrier, suggesting that it may act at the cerebral endothelium. Mice with a dominant‐negative mutation of endothelial PPAR‐γ (E‐V290M) exhibit cerebrovascular dysfunction after a high fat diet. Therefore, to test the hypothesis that activation of endothelial PPAR‐γ supports BRG, we determined if BRG is impaired in E‐V290M compared to wild‐type (WT) littermates fed a normal diet. Arterial pressure (AP) and heart rate (HR) were measured by telemetry during a 12:12‐hr dark (D): light (L) cycle. Spontaneous BRG (sBRG) was determined by the sequence method. WT and E‐V290M exhibited circadian changes (*P<0.05) in mean AP (MAP), HR and sBRG (Table). Basal MAP and HR did not differ between groups. However, the L increment in sBRG was less in E‐V290M than in WT (0.18±0.08 vs 0.55±0.07 ms/mmHg, P<0.05), and sBRG was lower in E‐V290M than WT during the L ( † P<0.05). These findings support the hypothesis that endothelial PPAR‐γ, possibly in cerebral vessels, enhances BRG. Funded by AHA 2060630 and NIH ( HL062984 , HL088552 ).