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PMID: 12721100 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factor.

British journal of pharmacology ·Vol. 138 ·No. 8 ·2003-04-00 ·Pages 1451-8

Wihlborg AK, Malmsjö M, Eyjolfsson A, Gustafsson R, Jacobson K, Erlinge D

Abstract

1. The present study was aimed at examining P2 receptor-mediated vasodilatation in human vessels. The isometric tension was recorded in isolated segments of the human left internal mammary artery branches precontracted with 1 microM noradrenaline. 2. Endothelial denudation abolished the dilator responses. 3. The selective P2Y(1) agonist, 2-MeSADP, induced a potent vasodilatation (pEC(50)=6.9+/-0.1). The P2Y(1) antagonist of 10 microM, MRS 2216, shifted the 2-MeSADP concentration-response curve 1.1 log units to the right. The combined P2Y(1) and P2X agonist, 2-MeSATP, stimulated a dilatation with a potency similar to that of 2-MeSADP. Furthermore, MRS 2216 had a similar antagonistic effect on both 2-MeSATP and 2-MeSADP indicating that P2X receptors do not mediate vasodilatation. 4. Both the P2Y(2/4) agonist, UTPgammaS and the P2Y(6) agonist, UDPbetaS, stimulated potent dilatations (pEC(50)=7.8+/-0.4 for UTPgammaS and 8.4+/-0.2 for UDPbetaS). 5. The 2-MeSADP-induced nitric oxide (NO)-mediated dilatation was studied in the presence of 10 micro M indomethacin, 50 nM charybdotoxin and 1 microM apamin. The involvement of the endothelium-derived hyperpolarising factor (EDHF) was investigated in the presence of 0.1 mM L-NOARG and indomethacin. The involvement of prostaglandins was investigated in the presence of L-NOARG, charybdotoxin and apamin. Both NO, EDHF and prostaglandins mediated 2-MeSADP dilatation with similar efficacy (E(max)=25+/-5% for NO, 25+/-6% for EDHF and 27+/-5% for prostaglandins). 6. In conclusion, extracellular nucleotides induce endothelium-derived vasodilatation in human vessels by stimulating P2Y(1), P2Y(2/4) and P2Y(6) receptors, while P2X receptors are not involved. Endothelial P2Y receptors mediate dilatation by release of EDHF, NO and prostaglandins.

MeSH Terms
Aged Biological Factors/physiology Dose-Response Relationship, Drug Extracellular Fluid/drug effects,physiology Female Humans In Vitro Techniques Male Mammary Arteries/drug effects,physiology Middle Aged Nitric Oxide/physiology Prostaglandins/physiology Receptors, Purinergic P2/physiology Thionucleotides/pharmacology,physiology Vasodilation/drug effects,physiology
Chemicals
Biological Factors Prostaglandins Receptors, Purinergic P2 Thionucleotides endothelium-dependent hyperpolarization factor Nitric Oxide
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wihlborg Anna-Karin
Department of Cardiology, Biomedical Center C12, Lund University, Sweden.
Malmsjö Malin
Eyjolfsson Atli
Gustafsson Ronny
Jacobson Kenneth
Erlinge David
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0705186
Published
2003-04-00
Pages
1451-8
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1573798
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjp.0705186 PMC Full Text View journal details
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