title: Endothelium modulates anion channel-dependent aortic contractions to iodide.
abstract: Anion currents contribute to vascular smooth muscle (VSM) membrane potential. The substitution of extracellular chloride (Cl) with iodide (I) or bromide (Br) initially inhibited and then potentiated isometric contractile responses of rat aortic rings to norepinephrine. Anion substitution alone produced a small relaxation, which occurred despite a lack of active tone and minimal subsequent contraction of endothelium-intact rings (4.2 +/- 1.2% of the response to 90 mM KCl). Endothelium-denuded rings underwent a similar initial relaxation but then contracted vigorously (I > Br). Responses to 130 mM I (93.7 +/- 1.9% of 90 mM KCl) were inhibited by nifedipine (10(-6) M), niflumic acid (10(-5) M), tamoxifen (10(-5) M), DIDS (10(-4) M), and HCO(-)(3)-free buffer (HEPES 10 mM) but not by bumetanide (10(-5) M). Intact rings treated with N(omega)-nitro-L-arginine (10(-4) M) responded weakly to I (15.5 +/- 2.1% of 90 mM KCl), whereas hemoglobin (10(-5) M), indomethacin (10(-6) M), 17-octadecynoic acid (10(-5) M), and 1H-[1,2, 4]oxadiazole[4,3-a]quinoxalin-1-one (10(-6) M) all failed to augment the response of intact rings to I. We hypothesize that VSM takes up I primarily via an anion exchanger. Subsequent I efflux through anion channels having a selectivity of I > Br > Cl produces depolarization. In endothelium-denuded or agonist-stimulated vessels, this current is sufficient to activate voltage-dependent calcium channels and cause contraction. Neither nitric oxide nor prostaglandins are the primary endothelial modulator of these anion channels. If they are regulated by an endothelium-dependent hyperpolarizing factor it is not a cytochrome P-450 metabolite.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. fred-lamb@uiowa.edu
authors.forename: F S
authors.initials: FS
authors.lastname: Lamb
authors.forename: T J
authors.initials: TJ
authors.lastname: Barna
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001965:Bromides / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D017670:Sodium Compounds / Q000494:pharmacology; D012974:Sodium Iodide / Q000494:pharmacology*; D013463:Sulfuric Acid Esters / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D001965:Bromides; D002121:Calcium Channel Blockers; D018118:Chloride Channels; D004791:Enzyme Inhibitors; D007473:Ion Channels; D017670:Sodium Compounds; D013463:Sulfuric Acid Esters; D012965:Sodium Chloride; D011189:Potassium Chloride; D012974:Sodium Iodide; D009543:Nifedipine; C027938:sodium bromide; C033522:methyl sulfate; D009638:Norepinephrine