Vascular effects of poly-N-acetylglucosamine in isolated rat aortic rings.
BACKGROUND
[corrected] Poly-N-acetylglucosamine (p-GlcNAc) is a secretion of marine diatoms that is known to be useful in controlling bleeding. As a component of promoting hemostasis, p-GlcNAc is thought to exert vasoconstrictor effects in arteries. The present study was undertaken to determine whether p-GlcNAc induced a significant vasoconstrictor effect and, if so, what the mechanism of this effect might be.


METHODS
We examined vascular effects of p-GlcNAc on isolated aortic rings obtained from Sprague-Dawley rats. The rings were suspended in organ baths and precontracted with U46619, a thromboxane A2 mimetic.


RESULTS
p-GlcNAc produced a concentration-dependent vasoconstriction over the range of 14 to 100 microg/ml. At a concentration of 100 microg/ml, p-GlcNAc significantly contracted aortic rings by 133 +/- 20 mg of developed force (P < 0.01). Neither a deacetylated derivative of p-GlcNAc nor a structurally related macromolecule, chitin, contracted rat aortic rings, indicating a specificity for p-GlcNAc. The vasoconstriction to p-GlcNAc was totally abolished in deendothelialized rat aortic rings, suggesting that an endothelial component is essential to the vasoconstriction. Pretreatment with the endothelin ET(A) receptor antagonist, JKC-301 (0.5 and 1 microM), significantly diminished p-GlcNAc-induced vasoconstriction by 57 to 61% (P < 0.01). However, p-GlcNAc did not significantly diminish nitric oxide release from rat aortic endothelium.


CONCLUSIONS
These results provide evidence that p-GlcNAc significantly contracts isolated rat aortic rings via an endothelium-dependent mechanism, partly via enhancement of endothelin-1 release from endothelial cells.
Ikeda
Yasuhiko
Y
Department of Physiology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Young
Lindon H
LH
Vournakis
John N
JN
Lefer
Allan M
AM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000117:Acetylglucosamine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011134:Polysaccharides; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; C113831:poly-N-acetyl glucosamine; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019331:NG-Nitroarginine Methyl Ester; D000117:Acetylglucosamine