title: Nitric oxide synthase inhibitors do not alter functional hyperemia in canine skeletal muscle.
abstract: To test the hypothesis that endothelium-derived products contribute to functional hyperemia in skeletal muscle, we infused nitric oxide synthase inhibitors, either 200 microM N omega-nitro-L-arginine (NNA) (N = 4) or 1 mM N gamma-monomethyl-L-arginine (NMMA) (N = 4), before and during 6 min of 4 Hz stimulation of canine gastrocnemius in situ. We infused saline (N = 4) as a control. NNA significantly decreased steady-level resting flow by 3.8 +/- 0.4 mL.kg-1.s-1. The increase in flow from rest to 5 min of stimulation was not changed by the nitric oxide synthase inhibitors. We also stimulated muscles for 60 min either with saline infusion (N = 4) or with the infusion of saline during the first 15 min and NNA for the remaining 45 min (n = 4). There was no difference in the flow during contractions. To clarify the effect of these inhibitors on canine vessels, we challenged rings of canine femoral artery with and without endothelium with acetylcholine and bradykinin (both 1 microM) before and after the addition of NNA and NMMA (both 10 microM). The nitric oxide synthase inhibitors decreased the relaxation accompanying acetylcholine. Both inhibitors caused only endothelium-intact rings to contract. Thus, the presence of a nitric oxide synthase inhibitor identified an endothelium-dependent contribution to the regulation of blood flow to skeletal muscle at rest but had no effect on functional hyperemia.
authors.affiliation: School of Human Biology, University of Guelph, ON, Canada.
authors.forename: J K
authors.initials: JK
authors.lastname: Barclay
authors.forename: N E
authors.initials: NE
authors.lastname: Woodley
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004285:Dogs; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006940:Hyperemia / Q000188:drug therapy*; D008297:Male; D009132:Muscles / Q000098:blood supply*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010101:Oxygen Consumption; D014661:Vasoconstriction / Q000187:drug effects; D019323:omega-N-Methylarginine
chemical_list: D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine; D001920:Bradykinin