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

被引:37
|
作者
Rutkai, Ibolya [1 ]
Feher, Attila [1 ]
Erdei, Nora [1 ]
Henrion, Daniel [2 ]
Papp, Zoltan [1 ]
Edes, Istvan [1 ]
Koller, Akos [3 ,4 ]
Kaley, Gabor [3 ]
Bagi, Zsolt [1 ,3 ]
机构
[1] Univ Debrecen, Inst Cardiol, Div Clin Physiol, H-4012 Debrecen, Hungary
[2] Univ Angers, CNRS, UMR 6214, INSERM,U771, F-49045 Angers, France
[3] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA
[4] Univ Pecs, Dept Pathophysiol & Gerontol, Pecs, Hungary
关键词
Diabetes; Hypertension; Arteriole; Prostanoid; EP receptor; SMOOTH-MUSCLE; PROSTANOID RECEPTORS; CORONARY ARTERIOLES; HYPERTENSION; RAT; RESISTANCE; CYCLOOXYGENASE-2; ENDOTHELIUM; INDUCTION; COX-2;
D O I
10.1093/cvr/cvp098
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (similar to 90 mu 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 mu M), 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.
引用
收藏
页码:148 / 154
页数:7
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