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Vascular hypercontractility to endothelin 1 in mice lacking endothelial PPARG
Author(s) -
Lange Willem Jacobus,
Beyer Andreas M.,
Halabi Carmen M.,
Sigmund Curt D.
Publication year - 2008
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.22.1_supplement.968.12
Subject(s) - peroxisome proliferator activated receptor gamma , medicine , endocrinology , vasodilation , vasoconstriction , endothelin receptor , endothelins , receptor , blood pressure , peroxisome proliferator activated receptor , chemistry
Peroxisome proliferator‐activated receptor gamma (PPARG), a ligand‐activated nuclear hormone receptor, plays an important role in modulating blood pressure. This is evidenced by observations that thiazolidinediones, synthetic PPARG ligands used as antidiabetic drugs, lower blood pressure, while certain PPARG dominant negative (DN) mutations cause diabetes and early onset severe hypertension in humans. As PPARG is expressed in the vasculature, we postulated that it may exert its effect on blood pressure by modulating vascular function and reactivity. In order to test this hypothesis, we generated mice in which PPARG is knocked out in the endothelium (PPARG−/−), using the Cre‐LoxP system. Vascular function was assessed by studying the response of aortas from ePPARG−/− mice to an array of vasodilators and constrictors under baseline conditions. Vasorelaxation in response to acetylcholine and sodium nitroprusside, as well as vasoconstriction to serotonin and protaglandin F2a were normal. Endothelin 1 (ET‐1) mediated vasoconstriction was, however, significantly enhanced in ePPARG−/− mice. This finding is in step with high fat diet‐induced hypertension in ePPARG−/− mice reported previously, as well as findings that DN PPARG mutations cause ET‐1 mediated hypercontractility. Together these findings indicate that endothelial PPARG may play an essential role in modulating vascular reactivity to ET‐1.