Endothelium modulates anion channel-dependent aortic contractions to iodide

Anion currents contribute to vascular smooth muscle (VSM) membrane potentia l. The substitution of extracellular chloride (Cl) with iodide (I) or bromi de (Br) initially inhibited and then potentiated isometric contractile resp onses of rat aortic rings to norepinephrine. Anion substitution alone produ ced a small relaxation, which occurred despite a lack of active tone and mi nimal subsequent contraction of endothelium-intact rings (4.2 +/- 1.2% of t he response to 90 mM KCl). Endothelium-denuded rings underwent a similar in itial relaxation but then contracted vigorously (I > Br). Responses to 130 mM I (93.7 +/- 1.9% of 90 mM KCI) were inhibited by nifedipine (10(-6) M), niflumic acid (10(-5) M), tamoxifen (10-5 M), DIDS (10(-4) M), and HCO3--fr ee buffer (HEPES 10 mM) but not by bumetanide (10(-5) M). Intact rings trea ted with N-omega-nitro-L-arginine (10(-4) M) responded weakly to I(15.5 +/- 2.1% of 90 mM KCI), 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) Mi all failed to augment the response of intact rings to I. We hypothesize that VSM takes up I primarily via an anion exchanger. Subseq uent I efflux through anion channels having a selectivity of I > Br > Cl pr oduces 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 pri mary endothelial modulator of these anion channels. If they are regulated b y an endothelium-dependent hyperpolarizing factor it is not a cytochrome P- 450 metabolite.