title: Regular slow wave flowmotion in skeletal muscle is not determined by nitric oxide and endothelin.
abstract: In a previous study we showed that the generation of regular slow wave flowmotion (rSWFM, 1-3 cycles per minute) in skeletal muscle of anesthetized rats was related to local changes of arterial pressure and microcirculatory blood flow (MBF), which suggests an involvement of pressure- or flow-induced mechanisms. The present experiments were designed to test the role of flow-dependent endothelial autacoids, such as nitric oxide (NO) and endothelin, in the generation of SWFM. The effects of NO-donor sodium nitroprusside (SNP), the partly NO-dependent metabolite adenosine (ADO), the NO-synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and the mixed endothelin receptor blocker bosentan (BOS) were analyzed. MBF and rSWFM were assessed by laser Doppler flowmetry. rSWFM appeared in 7 out of 14 preparations after ADO (200 microg/kg/min), but not after SNP (100 microg/kg/min), L-NAME (30 mg/kg iv), and BOS (10 mg/kg iv). Its occurrence was associated with a significant decrease in arterial pressure to 50 +/- 3% (mean +/- SEM) of the baseline, provided that MBF was not enhanced. When given after induction of rSWFM by a 25% hemorrhage, SNP (50 microg/kg/min) totally abolished rSWFM and ADO (100 microg/kg/min) reduced rSWFM frequency from 2.17 +/- 0.08 to 1.72 +/- 0.08 cycles per minute (cpm) (P < 0.05), whereas the frequency was not affected by the other drugs. ADO, l-NAME (30 mg/kg iv), and BOS (10 mg/kg iv) lead to changes in rSWFM amplitude which showed a drug-independent negative correlation to changes in both MAP and MBF (R(2) = 0.61, multiple regression) in the ranges of 57-176% of MAP before drug application, and 72-120% of MBF, respectively. We conclude that NO and endothelin are not involved in the generation of rSWFM. Our findings strongly suggest that the activity of rSWFM depends on a reduction of vascular wall tension and is inhibited by SNP.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Inselspital University Hospital, Berne, 3010, Switzerland. dominique.erni@insel.ch
authors.forename: D
authors.initials: D
authors.lastname: Erni
authors.forename: G H
authors.initials: GH
authors.lastname: Sigurdsson
authors.forename: A
authors.initials: A
authors.lastname: Banic
authors.forename: A M
authors.initials: AM
authors.lastname: Wheatley
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; 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; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D013449:Sulfonamides; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine; D000077300:Bosentan; D019331:NG-Nitroarginine Methyl Ester