L‐Tryptophan methyl ester Evokes Endothelium‐, Serotonin‐Independent Biphasic Vasoconstrictor and Vasodilator Responses in Rat Mesenteric Arterioles

L‐Tryptophan methyl ester Evokes Endothelium‐, Serotonin‐Independent Biphasic Vasoconstrictor and Vasodilator Responses in Rat Mesenteric Arterioles

The vascular effects of L‐tryptophan (L‐W) are unknown. The in vitro responses to L‐W and its cell permeant analog, L‐W methyl ester (L‐Wme), were compared in third order branches of mesenteric arterioles of 12 week old male Sprague Dawley rats. While L‐W had no effect, L‐Wme evoked concentration‐de...

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Bibliographic Details
Published in:The FASEB journal Vol. 24; no. S1; p. 575.6
Main Authors: Jadhav, Ashok B, Nadithe, Laxman Reddy, Balsevich, John, Akhtar, Jawed, Gopalakrishnan, Venkat
Format: Journal Article
Language:English
Published: Federation of American Societies for Experimental Biology 01-04-2010
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Summary:The vascular effects of L‐tryptophan (L‐W) are unknown. The in vitro responses to L‐W and its cell permeant analog, L‐W methyl ester (L‐Wme), were compared in third order branches of mesenteric arterioles of 12 week old male Sprague Dawley rats. While L‐W had no effect, L‐Wme evoked concentration‐dependent vasoconstriction (10 – 160 μM) followed by vasodilatation (300 μM – 2.5 mM) in both endothelium‐intact and endothelium‐denuded vessels. While 5‐HT antagonist, ketanserin (50 nM), shifted the responses to 5‐HT (EC50 Control 107 ± 10 nM vs. Treatment 32 ± 6 μM; p<0.001), it failed to affect the responses to L‐Wme. The inclusion of transient receptor potential channel (TRPC) blocker, 2‐aminoethoxy phenyl borate (10 μM) or the voltage‐gated Ca2+ channel blocker, verapamil (10 μM), abolished the bipahsic responses to L‐Wme. L‐Wme evoked (1 μM ‐ 2.5 mM) vasodilatation was more sensitive in potassium chloride depolarized (IC50 330 ± 19 μM; Imax 95%) than in phenylephrine constricted vessels (IC50 767 ± 23 μM; Imax 96%). These data suggest that the cell permeant amino acid, L‐Wme, exerts endothelium‐/serotonin‐independent responses that could be due to activation and blockade of Ca2+ influx occurring through either the TRPC and/or the voltage‐gated Ca2+ channels present on vascular smooth muscle cells of resistance type vessel. This confirms a direct role for L‐W analogs in the regulation of vascular smooth muscle tone.
ISSN:0892-6638
1530-6860
DOI:10.1096/fasebj.24.1_supplement.575.6