Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes.
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 E(2) (PGE(2)) receptor (EP1) increases skeletal muscle arteriolar tone and blood pressure in mice...
| Үндсэн зохиолчид: | , , , , , , , , |
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| Формат: | Journal article |
| Хэл сонгох: | English |
| Хэвлэсэн: |
2009
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| _version_ | 1826278990129659904 |
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| author | Rutkai, I Feher, A Erdei, N Henrion, D Papp, Z Edes, I Koller, A Kaley, G Bagi, Z |
| author_facet | Rutkai, I Feher, A Erdei, N Henrion, D Papp, Z Edes, I Koller, A Kaley, G Bagi, Z |
| author_sort | Rutkai, I |
| collection | OXFORD |
| description | 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 E(2) (PGE(2)) 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 ( 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. CONCLUSION: Activation of EP1 receptors increases arteriolar tone, which could contribute to the development of hypertension in the db/db mice. |
| first_indexed | 2024-03-06T23:52:09Z |
| format | Journal article |
| id | oxford-uuid:72f6b4ab-2edb-48bd-a72b-09d8473a12a2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:52:09Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:72f6b4ab-2edb-48bd-a72b-09d8473a12a22022-03-26T19:53:31ZActivation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:72f6b4ab-2edb-48bd-a72b-09d8473a12a2EnglishSymplectic Elements at Oxford2009Rutkai, IFeher, AErdei, NHenrion, DPapp, ZEdes, IKoller, AKaley, GBagi, Z 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 E(2) (PGE(2)) 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 ( 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. CONCLUSION: Activation of EP1 receptors increases arteriolar tone, which could contribute to the development of hypertension in the db/db mice. |
| spellingShingle | Rutkai, I Feher, A Erdei, N Henrion, D Papp, Z Edes, I Koller, A Kaley, G Bagi, Z Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. |
| title | Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. |
| title_full | Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. |
| title_fullStr | Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. |
| title_full_unstemmed | Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. |
| title_short | Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. |
| title_sort | activation of prostaglandin e2 ep1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes |
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