title: Acetylcholine-induced vasodilation may depend entirely upon NO in the femoral artery of young piglets.
abstract: 1 To characterize agonist-induced relaxation in femoral artery rings from young piglets, we compared the effect of a NOS-inhibitor N(omega)-nitro-L-arginine (L-NOARG), an NO-inactivator oxyhaemoglobin (HbO) and a soluble guanyl cyclase(sGC)-inhibitor 1H-[1,2,4]Oxadiazolo-[4,3,-alpha]quinoxalin-1-one (ODQ) on acetylcholine(ACh)-induced relaxation. The involvement of K(+) channel activation was studied on relaxations induced by ACh, the two NO donors sodium nitroprusside (SNP) and diethylamine (DEA) NONOate, and the cell membrane permeable guanosine 3'5' cyclic monophosphate (cGMP) analogue 8-Br-cGMP. 2 Full reversal of phenylephrine-mediated precontraction was induced by ACh (1 nM-1 microM) (pD(2) 8.2+/-0.01 and R(max) 98.7+/-0.3%). L-NOARG (100 microM) partly inhibited relaxation (pD(2) 7.4+/-0.02 and R(max) 49.6+/-0.8%). The L-NOARG/indomethacin(IM)-resistant response displayed characteristics typical for endothelium-derived hyperpolarizing factor (EDHF), being sensitive to a combination of the K(+) channel blockers charybdotoxin (CTX) (0.1 microM) and apamin (0.3 microM). 3 ODQ (10 microM) abolished relaxations induced by ACh and SNP. L-NOARG/IM-resistant relaxations to ACh were abolished by HbO (20 microM). 4 Ouabain (1 microM) significantly inhibited ACh-induced L-NOARG/IM-resistant relaxations and relaxations induced by SNP (10 microM) and 8-Br-cGMP (0.1 mM). A combination of ouabain and Ba(2+) (30 microM) almost abolished L-NOARG/IM-resistant ACh-induced relaxation (R(max) 7.7+/-2.5% vs 23.4+/-6.4%, with and without Ba(2+), respectively, P<0.05). 5 The present study demonstrates that in femoral artery rings from young piglets, despite an L-NOARG/IM-resistant component sensitive to K(+) channel blockade with CTX and apamin, ACh-induced relaxation is abolished by sGC-inhibition or a combination of L-NOARG and HbO. These findings suggest that relaxation can be fully explained by the NO/cGMP pathway.
authors.affiliation: Department of Physiology and Biomedical Engineering, Faculty of Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway. Ragnhild.Stoen@medisin.ntnu.no
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Støen
authors.forename: Kristin
authors.initials: K
authors.lastname: Lossius
authors.forename: Jan Olof G
authors.initials: JO
authors.lastname: Karlsson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine