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L‐Tryptophan ethyl ester dilates small mesenteric arteries by inhibition of voltage‐operated calcium channels in smooth muscle
Author(s) -
Jadhav Ashok,
Liang Wenbin,
Balsevich John,
Bastin Guillaume,
Kroetsch Jeff,
Heximer Scott,
Backx Peter H,
Gopalakrishnan Venkat
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01693.x
Subject(s) - phenylephrine , endocrinology , medicine , vasodilation , chemistry , aorta , mesenteric arteries , vascular smooth muscle , vasoconstriction , blood vessel , calcium , blood pressure , anatomy , artery , smooth muscle
BACKGROUND 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, (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 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.