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L‐Tryptophan methyl ester Evokes Endothelium‐, Serotonin‐Independent Biphasic Vasoconstrictor and Vasodilator Responses in Rat Mesenteric Arterioles
Author(s) -
Jadhav Ashok B,
Nadithe Laxman Reddy,
Balsevich John,
Akhtar Jawed,
Gopalakrishnan Venkat
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.575.6
Subject(s) - vasodilation , phenylephrine , vasoconstriction , verapamil , chemistry , ketanserin , vascular smooth muscle , endothelium , transient receptor potential channel , mesenteric arteries , pharmacology , serotonin , endocrinology , medicine , 5 ht receptor , smooth muscle , biochemistry , receptor , calcium , artery , organic chemistry , blood pressure
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 (EC 50 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 Ca 2+ 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 (IC 50 330 ± 19 μM; I max 95%) than in phenylephrine constricted vessels (IC 50 767 ± 23 μM; I max 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 Ca 2+ influx occurring through either the TRPC and/or the voltage‐gated Ca 2+ 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.