title: Flow induces dilatation in the femoral artery of uraemic rats but constriction in control rats.
abstract: BACKGROUND
  Pressure and flow are recognized as important modulators of vascular tone. In mildly uraemic rats, myogenic tone is increased in the femoral artery in the absence of hypertension compared with healthy control rats, but the effect of flow in the same experimental model remains unknown.
  
  
  METHODS
  Twelve male Wistar rats were rendered uraemic (U) by 5/6th nephrectomy or were concurrently sham operated as controls (C). After 8 weeks, isolated femoral arteries were mounted on a flow myograph, pressurized at 80 mmHg, and constricted by 40-50% of the lumen internal diameter (i.d.) by L-phenylephrine (1-10 micromol/l). Flow was initiated (0-207 microl/min) in six steps every 5 min and changes in i.d. recorded. N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (0.1 mmol/l) and 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (1 micromol/l) were applied extraluminally and the flow protocol repeated.
  
  
  RESULTS
  The baseline pre-constricted at 80 mmHg i.d. was significantly smaller in the U (U 255+/-21 microm vs C 365+/-36 microm, P<0.03). At all steps, flow elicited a dilatation in the U and a constriction in the C (U+ 24+/-8% vs C-17+/-5%, P<0.01). When L-NAME and ODQ were applied, a significant basal reduction in i.d. was observed in the C only (C 365+/-36 microm vs C+ L-NAME & ODQ 182+/-18 microm, P<0.01; U 255+/- 21 microm vs U+L-NAME & ODQ 240+/-11 microm, P=n.s.). Furthermore, in the U there was no significant blunting to dilatation during flow (+9+/-4%).
  
  
  CONCLUSIONS
  Flow elicited a constriction in controls, but a marked dilatation in uraemic roots which was not entirely nitric oxide dependent. These results suggest that other mediators such as prostacyclin or endothelium-dependent hyperpolarizing factor, or changes in the vascular smooth muscle may contribute to flow-induced dilatation in mild experimental uraemia.
authors.affiliation: Anthony Raine Research Laboratories, St Bartholomew's Hospital, Guys, Kings & St Thomas' Hospitals, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Savage
authors.forename: R M
authors.initials: RM
authors.lastname: Tribe
authors.forename: M M
authors.initials: MM
authors.lastname: Yaqoob
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D004573:Electrolytes / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006454:Hemoglobins / Q000032:analysis; D008297:Male; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014511:Uremia / Q000097:blood / Q000503:physiopathology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004573:Electrolytes; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D010069:Oxadiazoles; D011810:Quinoxalines; D019331:NG-Nitroarginine Methyl Ester