title: Endothelium-derived hyperpolarizing factor and potassium use different mechanisms to induce relaxation of human subcutaneous resistance arteries.
abstract: This investigation examined the hypothesis that release of K(+) accounts for EDHF activity by comparing relaxant responses produced by ACh and KCl in human subcutaneous resistance arteries. Resistance arteries (internal diameter 244+/-12 microm, n=48) from human subcutaneous fat biopsies were suspended in a wire myograph. Cumulative concentration-response curves were obtained for ACh (10(-9) - 3x10(-5) M) and KCl (2.5 - 25 mM) following contraction with noradrenaline (NA; 0.1 - 3 microM). ACh (E(max) 99.07+/-9.61%; -LogIC(50) 7.03+/-0.22; n=9) and KCl (E(max) 74.14+/-5.61%; -LogIC(50) 2.12+/-0.07; n=10)-induced relaxations were attenuated (P<0.0001) by removal of the endothelium (E(max) 8.21+/-5.39% and 11.56+/-8.49%, respectively; n=6 - 7). Indomethacin (10 microM) did not alter ACh-induced relaxation whereas L-NOARG (100 microM) reduced this response (E(max) 61.7+/-3.4%, P<0.0001; n=6). The combination of ChTx (50 nM) and apamin (30 nM) attenuated the L-NOARG-insensitive component of ACh-induced relaxation (E(max): 15.2+/-10.5%, P<0.002, n=6) although these arteries retained the ability to relax in response to 100 microM SIN-1 (E(max) 127.6+/-13.0%, n=3). Exposure to BaCl(2) (30 microM) and Ouabain (1 mM) did not attenuate the L-NOARG resistant component of ACh-mediated relaxation (E(max), 76.09+/-8.92, P=0.16; n=5). KCl-mediated relaxation was unaffected by L-NOARG+indomethacin (E(max); 68.1+/-5.6%, P=0.33; n=5) or the combination of L-NOARG/indomethacin/ChTx/apamin (E(max); 86.61+/-14.02%, P=0.35; n=6). In contrast, the combination of L-NOARG, indomethacin, ouabain and BaCl(2) abolished this response (E(max), 5.67+/-2.59%, P<0.0001, n=6). The characteristics of KCl-mediated relaxation differed from those of the nitric oxide/prostaglandin-independent component of the response to ACh, and were endothelium-dependent, indicating that K(+) does not act as an EDHF in human subcutaneous resistance arteries.
authors.affiliation: Department of Medical Sciences, Western General Hospital, University of Edinburgh, Edinburgh.
authors.forename: C A
authors.initials: CA
authors.lastname: McIntyre
authors.forename: C H
authors.initials: CH
authors.lastname: Buckley
authors.forename: G C
authors.initials: GC
authors.lastname: Jones
authors.forename: T C
authors.initials: TC
authors.lastname: Sandeep
authors.forename: R C
authors.initials: RC
authors.lastname: Andrews
authors.forename: A I
authors.initials: AI
authors.lastname: Elliott
authors.forename: G A
authors.initials: GA
authors.lastname: Gray
authors.forename: B C
authors.initials: BC
authors.lastname: Williams
authors.forename: J A
authors.initials: JA
authors.lastname: McKnight
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.forename: P W
authors.initials: PW
authors.lastname: Hadoke
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D017609:Barium Compounds / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D017609:Barium Compounds; D001685:Biological Factors; D002712:Chlorides; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; C024986:barium chloride; D018999:Charybdotoxin; D019335:Nitroarginine; D001030:Apamin; D010042:Ouabain; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine; D007213:Indomethacin