title: Nitric oxide-cGMP-mediated vasoconstriction and effects of acetylcholine in the branchial circulation of the eel.
abstract: Information about the presence and effects of nitric oxide (NO) in fish vasculature is scant and contradictory. We have studied the NO/cGMP system in the branchial circulation of the teleost Anguilla anguilla using a branchial basket preparation under basal conditions and cholinergic stimulation. The effects of endogenous and exogenous NO were tested with L-arginine, the nitric oxide synthase (NOS) substrate, and the NO donors 3-morpholinosydnonimine (SIN-1) and sodium nitroprusside (SNP), respectively. L-arginine (from 10(-11) to 10(-6) M) and the NO donors (starting from 10(-14) M) caused dose-dependent vasoconstriction. Conversely, in the ACh-pre-contracted preparations both donors elicited vasodilation. SIN-1-induced vasoconstriction was due to NO generation: it was increased by superoxide dismutase (SOD) and blocked by NO scavenger hemoglobin. Pre-treatment with sGC inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) inhibited the effects of SIN-1 and SNP. The stable cGMP analogue 8-bromo-guanosine 3',5'-cyclic monophosphate (8-Br cGMP) induced dose-dependent vasoconstriction. Unexpectedly, three NOS inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-monomethyl-L-arginine (L-NMMA), L-N(5)-(1-iminoethyl) ornithine (L-NIO), caused mild vasoconstriction. ACh caused vasoconstriction, but at pico- and nanomolar concentrations it caused mild but significant vasodilation in 40% of the preparations. Both responses, blocked by atropine and pirenzepine, required an intact endothelium. The ACh-induced vasoconstriction was substantially independent of a NO-cGMP mechanism.
authors.affiliation: Department of Cell Biology, University of Calabria, Arcavacata di Rende 87030 (CS), Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pellegrino
authors.forename: E
authors.initials: E
authors.lastname: Sprovieri
authors.forename: R
authors.initials: R
authors.lastname: Mazza
authors.forename: D J
authors.initials: DJ
authors.lastname: Randall
authors.forename: B
authors.initials: B
authors.lastname: Tota
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001934:Branchial Region / Q000098:blood supply* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004524:Eels / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005880:Gills / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D006454:Hemoglobins; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D000109:Acetylcholine