title: Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes.
abstract: OBJECTIVE
  Type 2 diabetes mellitus is frequently associated with hypertension, but the underlying mechanisms are not completely understood. We tested the hypothesis that activation of type 1 prostaglandin E(2) (PGE(2)) receptor (EP1) increases skeletal muscle arteriolar tone and blood pressure in mice with type 2 diabetes.
  
  
  RESULTS
  In 12-week-old, male db/db mice (with homozygote mutation in leptin receptor), systolic blood pressure was significantly elevated, compared with control heterozygotes. Isolated, pressurized gracilis muscle arterioles ( approximately 90 microm) of db/db mice exhibited an enhanced pressure- and angiotensin II (0.1-10 nM)-induced tone, which was reduced by the selective EP1 receptor antagonist, AH6809 (10 microM), to the level observed in arterioles of control mice. Exogenous application of PGE(2) (10 pM-100 nM) or the selective agonist of the EP1 receptor, 17-phenyl-trinor-PGE(2) (10 pM-100 nM), elicited arteriolar constrictions that were significantly enhanced in db/db mice (max: 31 +/- 4 and 29 +/- 5%), compared with controls (max: 20 +/- 2 and 14 +/- 3%, respectively). In the aorta of db/db mice, an increased protein expression of EP1, but not EP4, receptor was also detected by western immunoblotting. Moreover, we found that oral administration of the EP1 receptor antagonist, AH6809 (10 mg/kg/day, for 4 days), significantly reduced the systolic blood pressure in db/db, but not in control mice.
  
  
  CONCLUSIONS
  Activation of EP1 receptors increases arteriolar tone, which could contribute to the development of hypertension in the db/db mice.
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Rutkai
authors.forename: Attila
authors.initials: A
authors.lastname: Feher
authors.forename: Nora
authors.initials: N
authors.lastname: Erdei
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Papp
authors.forename: Istvan
authors.initials: I
authors.lastname: Edes
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
authors.forename: Gabor
authors.initials: G
authors.lastname: Kaley
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bagi
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology*; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000098:blood supply; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D014655:Vascular Resistance / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology
chemical_list: D011448:Prostaglandin Antagonists; C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D014662:Vasoconstrictor Agents; D044004:Xanthones; D000804:Angiotensin II; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D015232:Dinoprostone