title: Calcium-independent phospholipase A(2) plays a key role in the endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat.
abstract: Phospholipase A(2) (PLA(2)), a regulatory enzyme found in most mammalian cells, catalyzes the breakdown of membrane phospholipids to arachidonic acid. There are two major cytosolic types of the enzyme, calcium-dependent (cPLA(2)) and calcium-independent (iPLA(2)) PLA(2). The present study investigated whether or not iPLA(2) plays a role in the endothelium-dependent contractions of the aorta of the spontaneously hypertensive rat and its normotensive counterpart, the Wistar-Kyoto rat. The presence of iPLA(2) in the endothelial cells was identified by using immunochemistry and immunoblotting. Aortic rings with and without the endothelium were suspended in organ chambers for isometric tension recording. The production of prostanoids was measured by using enzyme immunoassay kits. iPLA(2) was densely distributed in endothelial cells of the aorta of both strains. At 3 x 10(-6) M, the selective iPLA(2) inhibitor, bromoenol lactone (BEL), abrogated endothelium-dependent contractions induced by acetylcholine but not those evoked by the calcium ionophore A-23187. The effects of BEL were similar in the aortae of Wistar-Kyoto and spontaneously hypertensive rats. The nonselective PLA(2) inhibitor quinacrine abolished the contractions triggered by both acetylcholine and A-23187, whereas the store-operated calcium channel inhibitor SKF-96365 prevented only the acetylcholine-induced contraction. The acetylcholine- but not the A-23187-induced release of 6-keto prostaglandin F(1alpha) was inhibited by BEL. The release of thromboxane B(2) by either acetylcholine or A-23187 was not affected by BEL. In conclusion, iPLA(2) plays a substantial role in the generation of endothelium-derived contracting factor evoked by acetylcholine.
authors.affiliation: Dept. of Pharmacology and Pharmacy, Univ. of Hong Kong, Hong Kong.
authors.forename: Michael S K
authors.initials: MS
authors.lastname: Wong
authors.forename: Ricky Y K
authors.initials: RY
authors.lastname: Man
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000201:enzymology*; D000001:Calcimycin / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology*; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D009281:Naphthalenes / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D054512:Phospholipases A2, Calcium-Independent / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D007093:Imidazoles; D007476:Ionophores; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; D011753:Pyrones; D014665:Vasodilator Agents; D000001:Calcimycin; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D054512:Phospholipases A2, Calcium-Independent; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D000109:Acetylcholine