Prostaglandin E2 exclusively constricts adult porcine large cerebral arteries via the phosphatidyl-inositol pathway through activation of EP1- and EP3-receptors on smooth muscle cells.
PGE2-induced constriction of adult porcine large cerebral arteries is mediated by the phosphatidyl-inositol pathway via activation of EP1- and EP3-receptors on smooth muscle cells.
Prostaglandin E2 (PGE2) has been shown to dilate and constrict the systemic vascular beds, including cerebral vessels. The exact mechanism of PGE2-induced cerebral vasoconstriction, however, is less clarified. The authors' preliminary studies showed that PGE2 exclusively constricted the adult porcine basilar arteries. The present study, therefore, was designed to examine the receptor mechanisms involved in PGE2-induced constriction of large cerebral arteries in the adult pig. Results from an in vitro tissue-bath study indicated that PGE2 and its agonists 17-phenyl trinor PGE2 (17-PGE2), sulprostone (EP1/EP3 receptor agonists), and 11-deoxy-16,16-dimethyl PGE2 (11-PGE2, 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 PGE2, 17-PGE2, 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-PGE2-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 EP3-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, PGE2 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.
Jadhav et al. (Wed,) conducted a other in Cerebral vasoconstriction. Prostaglandin E2 (PGE2) and agonists was evaluated on Constriction of large cerebral arteries. Prostaglandin E2 exclusively constricts adult porcine large cerebral arteries via the phosphatidyl-inositol pathway through activation of EP1- and EP3-receptors on smooth muscle cells.