Repository logo
 

Vascular effects of tryptophan

Date

2010-01-14

Journal Title

Journal ISSN

Volume Title

Publisher

ORCID

Type

Degree Level

Masters

Abstract

Previous studies have shown that L-tryptophan treatment has been known to reduce blood pressure (BP) in hypertensive rats. L-tryptophan is converted to serotonin (5-HT), a potent vasoconstrictor agonist. The direct vascular effects of L-tryptophan, an essential amino acid, and the mechanism that contributes to the fall in BP have not been fully explored. The present study aims to examine the direct vascular responses to both D- and L- tryptophan using perfused mesenteric vascular bed, an ex-vivo preparation that represents the resistance function of circulation. Perfusion was maintained at a constant flow rate (5 mL/min) with Krebs buffer (pH 7.4, 37°C) after isolation from 12 to 14 week old male Sprague-Dawley rats. The basal perfusion pressure (PP) (mean ± SEM) was 27 ± 3 mmHg. Inclusion of D- and L-isomers in the perfusion medium led to concentration-dependent increase in PP. While the maximal response (Eₘₐₓ) was similar, D-tryptophan (EC₅₀: 0.25 ± 0.12* µmol; Eₘₐₓ: 128 ± 8 mmHg) was more potent (lower EC₅₀ value; *p < 0.01) than L-tryptophan (EC₅₀: 0.79 ± 0.30 µmol; Eₘₐₓ: 141 ± 7 mmHg). Inclusion of increasing concentrations (2, 5 and 10 nM) of the 5-HT₂A selective antagonist, ketanserin, led to parallel right-ward shifts in the concentration-response curves to D- and L-tryptophan with restoration of their Eₘₐₓ. In contrast, the α1 selective agonist, methoxamine (30 µM), constricted preparations, both D- (IC₅₀: 0.94 ± 0.30* µmol; Iₘₐₓ: 96 ± 2%) and L-tryptophan (IC₅₀: 2.8 ± 1.0 µmol Imax: 88± 1%) evoked concentration-dependent vasodilatation, an effect that was resistant to blockade by either ketanserin or other 5-HT antagonists. Again, D-tryptophan was more potent than L-tryptophan in the presence of 5-HT antagonist (*p < 0.05). Neither the removal of endothelium nor incubation with selective inhibitors of dilatory mediators released from the endothelium, failed to alter the vasodilator responses to D- and L-tryptophan. In potassium chloride depolarized preparations, L-tryptophan evoked an additive vasoconstrictor response. The vasodilator responses to L-tryptophan persisted in the presence of glibenclamide, a KATP channel inhibitor, or tetraethyl ammonium, a BKCa channel inhibitor, or BaCl₂, a Kir channel inhibitor, or ouabain, a Na⁺-K⁺-ATPase pump inhibitor. These data confirm that the essential amino acid, L-tryptophan, as well as its D-isomer, evoke a biphasic vasoconstrictor and vasodilator responses in the resistance type mesenteric vascular bed. While the vasoconstrictor responses are mediated by activation of vascular 5-HT receptors, the endothelium-independent vasodilator responses are not linked to activation of vascular 5-HT receptors, vascular potassium channels, Na⁺-K⁺-ATPase pump or via inhibition of voltage-operated Ca²⁺-channels. Plasma concentration of L-tryptophan is about 90 - 120 µM. The endothelium/5-HT independent direct vasodilator responses characterized here for the first time could account for the antihypertensive/ BP lowering effect of L-tryptophan reported earlier by other laboratories.

Description

Keywords

Hypertension, Tryptophan, Endothelium, Vascular Smooth Muscle, Mesenteric Vascular Bed

Citation

Degree

Master of Science (M.Sc.)

Department

Pharmacology

Program

Pharmacology

Citation

Part Of

item.page.relation.ispartofseries

DOI

item.page.identifier.pmid

item.page.identifier.pmcid