EP1- and EP3-receptors mediate prostaglandin E2-induced constriction of porcine large cerebral arteries

被引:58
作者
Jadhav, V
Jabre, A
Lin, SZ
Lee, TJF
机构
[1] So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA
[2] Boston Univ, Med Ctr, Dept Neurosurg, Boston, MA 02215 USA
[3] Tzu Chi Univ, Tzu Chi Gen Hosp, Coll Life Sci, Neuromed Sci Ctr,Ctr Vasc Med, Hualien, Taiwan
关键词
prostaglandin E-2 (PGE(2)); porcine cerebral arteries; vasoconstriction; smooth muscle; EP1- and EP3-receptors;
D O I
10.1097/01.WCB.0000139446.61789.14
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Prostaglandin E-2 (PGE(2)) has been shown to dilate and constrict the systemic vascular beds, including cerebral vessels. The exact mechanism of PGE(2)-induced cerebral vasoconstriction, however, is less clarified. The authors' preliminary studies showed that PGE(2) exclusively constricted the adult porcine basilar arteries. The present study, therefore, was designed to examine the receptor mechanisms involved in PGE(2) induced constriction of large cerebral arteries in the adult pig. Results from an in vitro tissue-bath study indicated that PGE(2) and its agonists 17-phenyl trinor PGE(2) (17-PGE(2)), sulprostone (EP1/EP3 receptor agonists), and 11-deoxy-16,16-dimethyl PGE(2) (11-PGE(2,) an EP2/EP3 -receptor agonist) induced exclusive constriction, which was not affected by endothelium denudation or cold-storage denervation of perivascular nerves. The constriction induced by PGE(2) 17-PGE(2), and sulprostone, but not by potassium chloride, was blocked by SC- 19220 (a selective EP1-receptor antagonist), AH-6809 (an EP1/EP2 -receptor antagonist), and U-73122 and neomycin (phospholipase C inhibitors). AH-6809, however, did not affect 11-PGE(2)-induced contraction. These results suggest that the contraction was not mediated by the EP2-receptor, but was mediated by EP1- and EP3-receptors. Furthermore, EP1-receptor immunoreactivities were found across the entire medial smooth muscle layers, whereas EP1-receptor immunoreactivities were limited to the outer smooth muscle layer toward the adventitia. Western blotting also showed the presence of EP1- and EP3-receptor proteins in cultured primary cerebral vascular smooth muscle cells. In conclusion, PGE(2) exclusively constricts the adult porcine large cerebral arteries. This constriction is mediated by phosphatidyl-inositol pathway via activation of EP1- and EP3 receptors located on the smooth muscle cells. These two receptor subtypes may play important roles in physiologic and pathophysiologic control of cerebral vascular tone.
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收藏
页码:1305 / 1316
页数:12
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