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Activation of EP1 prostaglandin E2 receptor enhances arteriolar tone and blood pressure in mice with type 2 diabetes mellitus
Author(s) -
Feher Attila,
Rutkai Ibolya,
Beleznai Timea,
Edes Istvan,
Bagi Zsolt
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.22.2_supplement.61
Subject(s) - endocrinology , medicine , receptor , agonist , prostaglandin e2 , blood pressure , type 2 diabetes , chemistry , receptor antagonist , prostaglandin , antagonist , diabetes mellitus
We tested the hypothesis that prostaglandin E2 (PGE2) via activating type 1 PGE2 (EP1) receptors increases arteriolar tone and enhances blood pressure in mice with type 2 diabetes (db/db mice). We found that db/db mice exhibited elevated blood pressure and enhanced myogenic tone of isolated, pressurized gracilis muscle arterioles, when compared to controls. In db/db mice the plasma level of PGE2 metabolites were markedly increased. We found that in db/db mice the enhanced arteriolar tone was reduced by the selective EP1 receptor antagonist, AH‐6809 (10μM) to the level observed in control mice. In gracilis arterioles application of PGE2 (10pM‐100nM) or the selective agonist of EP1 receptor, 17‐phenyl‐trinor‐PGE2 (10pM‐100nM) elicited constrictions that were significantly enhanced in db/db mice (max:31±4 and 29±5%), compared to those of controls (max:20±2 and 14±3%, respectively). In the aorta of db/db mice an increased EP1 receptor protein expression was detected by Western blot. Moreover, we found that oral administration of EP1 receptor antagonist, AH‐6809 (10mg/kg/day) significantly reduced systolic blood pressure in db/db mice, but did not affect blood pressure of control animals. Thus, we propose that an increased production of PGE2 in resistance vessels, via activating the EP1 receptors increases arteriolar tone and may elevate blood pressure of mice with type 2 diabetes.