title: Cellular mechanisms of endothelin in rabbit aorta.
abstract: The present studies were designed to investigate the cellular actions of endothelin in rabbit aorta. Endothelin produced concentration-dependent contraction of rabbit isolated aortic rings which was independent of the endothelium; the EC50 values were 6.1 and 5.6 nM for endothelium-intact and endothelium-denuded vascular rings, respectively. Endothelin (1 nM) did not induce the release or inhibit the effect of endothelium-derived relaxing factor in precontracted aortic rings. Removal of calcium from the external bathing medium reduced the maximal contractile response induced by endothelin (0.1 microM) by only 12%; however, addition of ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (0.1 mM) to the calcium-free medium produced a marked inhibition (approximately 75%) of endothelin-induced contraction. The dihydropyridine calcium channel antagonists nicardipine (1 microM) or nifedipine (1 microM), and also diltiazem (1 microM), had little or no effect on endothelin concentration-response curves. Contraction produced by endothelin (30 nM) was not associated with an alteration in the levels of cyclic 3',5'-adenosine monophosphate or cyclic 3',5-guanosine monophosphate in either endothelium-intact or endothelium-denuded aortic rings. Endothelin (1 nM-0.1 microM) produced concentration-dependent stimulation of phosphatidylinositol (Pl) turnover in aortic rings when exposed to tissues for periods greater than or equal to 15 min. Endothelin-induced stimulation of Pl turnover was unaffected by nicardipine (0.1 microM). In calcium-free medium (+0.1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) basal Pl turnover was reduced; however, endothelin (1 nM-0.1 microM) produced similar percentage increases over basal levels to those observed in the presence of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pennsylvania.
authors.forename: E H
authors.initials: EH
authors.lastname: Ohlstein
authors.forename: S
authors.initials: S
authors.lastname: Horohonich
authors.forename: D W
authors.initials: DW
authors.lastname: Hay
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D001685:Biological Factors / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D016232:Endothelins; D004730:Endothelium, Vascular / Q000032:analysis*; D009569:Nitric Oxide; D009712:Nucleotides, Cyclic / Q000032:analysis; D010455:Peptides / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001685:Biological Factors; D002121:Calcium Channel Blockers; D016232:Endothelins; D009712:Nucleotides, Cyclic; D010455:Peptides; D010716:Phosphatidylinositols; D009569:Nitric Oxide; D004533:Egtazic Acid; D011493:Protein Kinase C; D002118:Calcium