title: The roles of nitric oxide in dilating proximal and terminal arterioles of skeletal muscle during systemic hypoxia.
abstract: Indirect evidence suggests that dilatation evoked by systemic hypoxia in proximal and terminal arterioles of skeletal muscle is mediated by adenosine acting on A(1) receptors, but that the dilatation of proximal arterioles requires the presence of nitric oxide (NO), whereas that of terminal arterioles is mediated by NO. In the present study, we showed that primary and terminal arterioles of spinotrapezius muscle (diameters: 45 +/- 4 and 9 +/- 1 microm, respectively) in anaesthetised rats dilated by 15 +/- 7 and 48 +/- 24%, respectively, during hypoxia (breathing 12% O(2)). Inhibition of NO synthesis with intravenous nitro-L-arginine methyl ester attenuated these responses (to -2 +/- 3 and -4 +/- 4%, respectively). However, when a tonic level of NO was subsequently restored by infusion of NO donor, hypoxia evoked dilatation of primary arterioles (+24 +/- 8%) but not terminal arterioles (0 +/- 4%). The adenosine A(1) receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) (intravenous) attenuated this 'restored' primary arteriolar vasodilatation (to +6 +/- 3%). Similar results were obtained with 8% O(2). We propose that (1) proximal arteriolar dilatation evoked by systemic hypoxia depends on a background level of NO, which facilitates the action of adenosine on A(1) receptors, and (2) hypoxia-evoked dilatation of terminal arterioles is mediated by NO synthesised via A(1) receptor stimulation.
authors.affiliation: Department of Physiology, The Medical School, The University of Birmingham, Birmingham, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Edmunds
authors.forename: Janice M
authors.initials: JM
authors.lastname: Marshall
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation; D014970:Xanthines / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D058915:Purinergic P1 Receptor Antagonists; C110881:S-nitro-N-acetylpenicillamine; D014970:Xanthines; D009599:Nitroprusside; D009569:Nitric Oxide; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester