title: Effects of dietary salt loading on the responses of isolated rat mesenteric arteries to leptin.
abstract: BACKGROUND
  Leptin induces relaxation of vascular smooth muscle through an endothelium-dependent release of nitric oxide (EDNO) and administration of a high-salt diet reduces the relaxation of vessels to EDNO. We would, therefore, predict that salt loading would reduce the leptin-induced dilatation. However, in salt-loaded animals the relaxation to acetylcholine is maintained through an endothelial-dependent hypopolarizing factor instead of EDNO. These experiments were, therefore, designed to examine whether in salt-loaded animals the response to leptin would be reduced or whether, as for acetylcholine, an alternative mechanism would be substituted.
  
  
  METHODS
  Weanling rats were given diets containing either 0.4% (n = 10) or 8% (n = 9) sodium chloride for 4 weeks. They were then killed and a length of second order mesenteric artery was mounted in a perfusion myograph with diameter changes measured using a microscope-video tracking system. The vessels were preconstricted with norepinephrine and then the effects of graded concentrations of leptin were determined.
  
  
  RESULTS
  In vessels from the low salt animals leptin caused a dose-dependent dilatation (maximum change 31.4% +/- 5.8% of the initial norepinephrine-induced constriction) but in the high salt animals the change was only 3.4% +/- 1.1%. The nitric oxide synthase blocker Nomega-nitro-L-arginine methyl ester (L-NAME) abolished the responses, although responses could still be obtained in vessels from both groups to the NO donor, sodium nitroprusside.
  
  
  CONCLUSIONS
  These results indicate that salt loading to rats almost completely abolishes the vasodilatation to leptin. This implies endothelial disruption and, unlike the response to acetylcholine, no other vasodilator mechanism is implicated. This could provide a link between high salt intake and hypertension because the known increase in sympathetic activity caused by leptin would not be countered by a direct vasorelaxation.
authors.affiliation: Department of Physiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Jaffar
authors.forename: David S
authors.initials: DS
authors.lastname: Myers
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Hainsworth
authors.forename: Roger
authors.initials: R
authors.lastname: Hainsworth
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Drinkhill
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D020738:Leptin / Q000008:administration & dosage* / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D020738:Leptin; D020030:Nitric Oxide Donors; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine