L-Tryptophan ethyl ester dilates small mesenteric arteries by inhibition of voltage-operated calcium channels in smooth muscle

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DOIResolve DOI: http://doi.org/10.1111/j.1476-5381.2011.01693.x
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TypeArticle
Journal titleBritish Journal of Pharmacology
Volume166
Issue1
Pages232242; # of pages: 11
Subjectaorta; Ba²⁺ current; blood pressure; L-tryptophan; L-tryptophan ethyl ester; mesenteric artery; phenylephrine; potassium chloride; voltage-operated Ca²⁺ channel
AbstractBACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY 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, (Imax > 98%) tension responses to phenylephrine and KCl in an endothelium-independent manner in aorta (IC₅₀ 2 mM) and MA (IC₅₀ 17 μM). L-Wee evoked concentration-dependent inhibition of VOCC currents (IC₅₀ 12 μM; Imax 90%) in VSMC of MA. CONCLUSIONS AND IMPLICATIONS: 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.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada; NRC Plant Biotechnology Institute
Peer reviewedYes
NRC number54669
NPARC number21186093
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Record identifierfd990543-d078-43c9-b4f9-4815e9db850a
Record created2013-01-09
Record modified2017-03-23
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