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L-Tryptophan ethyl ester dilates small mesenteric arteries by inhibition of voltage-operated calcium channels in smooth muscle
| Content Provider | Scilit |
|---|---|
| Author | Jadhav, Ashok Liang, Wenbin Balsevich, John Bastin, Guillaume Kroetsch, Jeff Heximer, Scott Backx, Peter H. Gopalakrishnan, Venkat |
| Copyright Year | 2012 |
| Description | Journal: British Journal of Pharmacology 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⁻\ub9, 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 \u3bcM). L-Wee evoked concentration-dependent inhibition of VOCC currents (IC₅₀ 12 \u3bcM; 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.Peer reviewed: YesNRC publication: Ye |
| Related Links | http://europepmc.org/articles/pmc3415651?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415651/pdf http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01693.x/pdf |
| Ending Page | 242 |
| Page Count | 11 |
| Starting Page | 232 |
| e-ISSN | 14765381 |
| DOI | 10.1111/j.1476-5381.2011.01693.x |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 166 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2012-04-10 |
| Access Restriction | Open |
| Subject Keyword | Journal: British Journal of Pharmacology L‐tryptophan Ethyl Ester Mesenteric Artery Potassium Chloride Voltage‐operated Ca2+ Channel |
| Content Type | Text |
| Resource Type | Article |
