Characterization of endothelium-dependent relaxation independent of NO and prostaglandins in guinea pig coronary artery. 1998

A Yamanaka, and T Ishikawa, and K Goto
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.

In the presence of N omega-nitro-L-arginine and indomethacin, acetylcholine (ACh) induced endothelium-dependent relaxation in guinea pig coronary artery preconstricted with 9,11-dideoxy-9 alpha, 11 alpha-epoxymethano prostaglandin F2 alpha. Dexamethasone and arachidonyltrifluoromethyl ketone, inhibitors of phospholipase A2, and 17-octadecynoic acid, an inhibitor of cytochrome P450 epoxygenase, had no effect on the response to ACh. Although proadifen, which is used widely as an inhibitor of cytochrome P450-dependent enzymes, suppressed the ACh-induced relaxation, the drug also inhibited the relaxation induced by cromakalim, a K+ channel opener. In isolated smooth muscle cells of guinea pig coronary artery, proadifen, but not 17-octadecynoic acid, almost abolished delayed rectifier K+ current. Epoxyeicosatrienoic acids failed to relax the artery. Apamin and iberiotoxin, inhibitors of small- and large-conductance Ca(++)-activated K+ channels, respectively, did not affect the relaxation induced by ACh. A combination of charybdotoxin plus apamin, but not iberiotoxin plus apamin, abolished the response. However, the combination of charybdotoxin plus apamin had no effect on ACh-induced increase in intracellular free Ca++ concentration in endothelial cells. These results suggest that epoxyeicosatrienoic acids do not contribute to N omega-nitro-L-arginine/indomethacin-resistant relaxation induced by ACh in the guinea pig coronary artery. The present study also proposes that K+ channels on vascular smooth muscle cells, which both charybdotoxin and apamin must affect for inhibition to occur, are the target for endothelium-derived hyperpolarizing factor.

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010741 Phospholipases A Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D011453 Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Prostaglandin,Prostanoid,Prostanoids
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003331 Coronary Vessels The veins and arteries of the HEART. Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005231 Fatty Acids, Unsaturated FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds. Fatty Acids, Polyunsaturated,Polyunsaturated Fatty Acid,Unsaturated Fatty Acid,Polyunsaturated Fatty Acids,Acid, Polyunsaturated Fatty,Acid, Unsaturated Fatty,Acids, Polyunsaturated Fatty,Acids, Unsaturated Fatty,Fatty Acid, Polyunsaturated,Fatty Acid, Unsaturated,Unsaturated Fatty Acids
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea

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