Abstract
Aims:
The present study examined the hypothesis that prostaglandin E2 (PGE2) through activation of prostaglandin E (EP) receptor contributes to endothelium-dependent contractions.
Methods and results:
Western blotting revealed that the protein expression of EP1 receptor was significantly down-regulated in the aorta of the spontaneously hypertensive rat (SHR), but there was no significant difference in the expression of EP2, EP4, and total EP3 receptors between preparations of Wistar Kyoto rats (WKY) and SHR. Isometric tension studies showed that low concentrations of PGE2 caused endothelium-dependent relaxations in WKY but not in aortas of the SHR. High concentrations of PGE2 evoked contractions predominately through the activation of thromboxane-prostanoid (TP) receptors in the WKY, but involves the dual activation EP and TP receptors in the SHR. SQ29,548, BAYu3405 and Terutroban (TP receptor antagonists), and AH6809 (non-selective EP receptor antagonist) abolished, while SC19220 (preferential EP1 receptor antagonist) did not inhibit endothelium-dependent contractions. Both SC19220 and AH6809 significantly inhibited contractions to U46619 (TP receptor agonist).
Conclusion:
The present study demonstrates that the contraction caused by PGE2 in the SHR aorta is dependent on the activation of EP1 and TP receptors, but that endothelium-dependent contractions do not require the former. Thus, PGE2 is unlikely to be an endothelium-derived contracting factor in this artery. The ability of AH6809 to inhibit endothelium-dependent contractions can be attributed to its partial antagonism at TP receptors. Nevertheless, the impairment of PGE2-mediated relaxation may contribute to endothelial dysfunction in the aorta of the SHR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
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Animals
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Aorta, Thoracic / drug effects
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Aorta, Thoracic / metabolism*
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Aorta, Thoracic / physiopathology
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Blotting, Western
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Bridged Bicyclo Compounds, Heterocyclic
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Carbazoles / pharmacology
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Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / pharmacology
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Dinoprostone / analogs & derivatives
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Dinoprostone / metabolism*
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Dinoprostone / pharmacology
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism*
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Endothelium, Vascular / physiopathology
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Fatty Acids, Unsaturated
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Hydrazines / pharmacology
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Hypertension / metabolism*
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Hypertension / physiopathology
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Immunohistochemistry
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Naphthalenes / pharmacology
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Phenylephrine / pharmacology
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Potassium Chloride / pharmacology
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Propionates / pharmacology
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Prostaglandin Antagonists / pharmacology
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Rats
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Rats, Inbred SHR
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Rats, Inbred WKY
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Receptors, Prostaglandin E / antagonists & inhibitors
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Receptors, Prostaglandin E / metabolism*
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Receptors, Prostaglandin E, EP1 Subtype
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Receptors, Thromboxane / antagonists & inhibitors
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Receptors, Thromboxane / metabolism*
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Sulfonamides / pharmacology
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Vasoconstriction* / drug effects
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Vasoconstrictor Agents / pharmacology
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Vasodilation
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Xanthones / pharmacology
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Carbazoles
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Fatty Acids, Unsaturated
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Hydrazines
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Naphthalenes
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Propionates
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Prostaglandin Antagonists
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Ptger1 protein, rat
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Receptors, Prostaglandin E
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Receptors, Prostaglandin E, EP1 Subtype
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Receptors, Thromboxane
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Sulfonamides
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Vasoconstrictor Agents
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Xanthones
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Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide
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Phenylephrine
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6-isopropoxy-9-oxoxanthene-2-carboxylic acid
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sulprostone
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Potassium Chloride
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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SQ 29548
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terutroban
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Dinoprostone
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ramatroban