Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes

Ibolya Rutkai, Attila Feher, Nora Erdei, Daniel Henrion, Zoltan Papp, Istvan Edes, Akos Koller, Gabor Kaley, Zsolt Bagi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Aims: 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 E2 (PGE2) receptor (EP1) increases skeletal muscle arteriolar tone and blood pressure in mice with type 2 diabetes. Methods and 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 (∼90 m) 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 M), to the level observed in arterioles of control mice. Exogenous application of PGE2 (10 pM-100 nM) or the selective agonist of the EP1 receptor, 17-phenyl-trinor-PGE2 (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. Conclusion: Activation of EP1 receptors increases arteriolar tone, which could contribute to the development of hypertension in the db/db mice.

Original languageEnglish (US)
Pages (from-to)148-154
Number of pages7
JournalCardiovascular Research
Volume83
Issue number1
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

Fingerprint

Dinoprostone
Type 2 Diabetes Mellitus
Blood Pressure
Arterioles
Prostaglandin Receptors
Hypertension
Leptin Receptors
Homozygote
Heterozygote
Constriction
Angiotensin II
Oral Administration
Aorta
Skeletal Muscle
Western Blotting
Pressure
Mutation

Keywords

  • Arteriole
  • Diabetes
  • EP receptor
  • Hypertension
  • Prostanoid

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. / Rutkai, Ibolya; Feher, Attila; Erdei, Nora; Henrion, Daniel; Papp, Zoltan; Edes, Istvan; Koller, Akos; Kaley, Gabor; Bagi, Zsolt.

In: Cardiovascular Research, Vol. 83, No. 1, 01.07.2009, p. 148-154.

Research output: Contribution to journalArticle

Rutkai, Ibolya ; Feher, Attila ; Erdei, Nora ; Henrion, Daniel ; Papp, Zoltan ; Edes, Istvan ; Koller, Akos ; Kaley, Gabor ; Bagi, Zsolt. / Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. In: Cardiovascular Research. 2009 ; Vol. 83, No. 1. pp. 148-154.
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AU - Feher, Attila

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AU - Papp, Zoltan

AU - Edes, Istvan

AU - Koller, Akos

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