title: L-tryptophan ethyl ester dilates small mesenteric arteries by inhibition of voltage-operated calcium channels in smooth muscle.
abstract: OBJECTIVE
  L-tryptophan (L-W) is a precursor of the vasoconstrictor, 5-HT. However, acute administration of L-W ethyl ester (L-Wee) lowered blood pressure. The mechanism of action is unknown. This study compares the vascular effects of L-W and L-Wee in intact animals, isolated aortic rings, small mesenteric arteries (MA) and explores possible mechanisms by studies in vascular smooth muscle cells (VSMC) of MA.
  
  
  METHODS
  Effects of L-W or L-Wee (5-50 mg kg(-1) , i.v.) on mean arterial pressure (MAP) and heart rate (HR) were determined in male Sprague-Dawley rats. The effects of L-W and L-Wee on basal tone and of phenylephrine- or KCl-induced contractions of aortic and MA rings were assessed. Effects of L-Wee and L-W on voltage-operated calcium channels (VOCC) of VSMC of MA were also examined in patch-clamp studies.
  
  
  RESULTS
  Administration of L-Wee, but not L-W, evoked a rapid and transient dose-dependent decrease in MAP and HR. While both agents failed to affect basal tone, L-Wee decreased, concentration-dependently, (I(max) > 98%) tension responses to phenylephrine and KCl in an endothelium-independent manner in aorta (IC(50) 2 mM) and MA (IC(50) 17 µM). L-Wee evoked concentration-dependent inhibition of VOCC currents (IC(50) 12 µM; I(max) 90%) in VSMC of MA.
  
  
  CONCLUSIONS
  Esterified L-W (L-Wee), but not L-W, preferentially relaxed resistance vessels rather than conduit vessels. These effects were associated with blockade of VOCC by L-Wee. Our findings suggest that the falls in MAP and HR induced by L-Wee were due to blockade of VOCC by L-Wee.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jadhav
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liang
authors.forename: John
authors.initials: J
authors.lastname: Balsevich
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bastin
authors.forename: Jeff
authors.initials: J
authors.lastname: Kroetsch
authors.forename: Scott
authors.initials: S
authors.lastname: Heximer
authors.forename: Peter H
authors.initials: PH
authors.lastname: Backx
authors.forename: Venkat
authors.initials: V
authors.lastname: Gopalakrishnan
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010656:Phenylephrine; C025166:tryptophan ethyl ester; D011189:Potassium Chloride; D014364:Tryptophan