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

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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 muM noradrenaline.
2. Endothelial denudation abolished the dilator responses.
3. The selective P2Y1 agonist, 2-MeSADP, induced a potent vasodilatation (pEC50=6.9plusminus0.1). The P2Y1 antagonist of 10 muM, MRS 2216, shifted the 2-MeSADP concentration-response curve 1.1 log units to the right. The combined P2Y1 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 P2Y2/4 agonist, UTPitalic gammaS and the P2Y6 agonist, UDPbetaS, stimulated potent dilatations (pEC50=7.8plusminus0.4 for UTPitalic gammaS and 8.4plusminus0.2 for UDPbetaS).
5. The 2-MeSADP-induced nitric oxide (NO)-mediated dilatation was studied in the presence of 10 muM indomethacin, 50 nM charybdotoxin and 1 muM apamin. The involvement of the endothelium-derived hyperpolarising factor (EDHF) was investigated in the presence of 0.1 mML-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 (Emax=25plusminus5% for NO, 25plusminus6% for EDHF and 27plusminus5% for prostaglandins).
6. In conclusion, extracellular nucleotides induce endothelium-derived vasodilatation in human vessels by stimulating P2Y1, P2Y2/4 and P2Y6 receptors, while P2X receptors are not involved. Endothelial P2Y receptors mediate dilatation by release of EDHF, NO and prostaglandins

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Farmakologi och toxikologi

Nyckelord

Originalspråkengelska
Sidor (från-till)1451-1458
TidskriftBritish Journal of Pharmacology
Volym138
Utgivningsnummer8
StatusPublished - 2003
PublikationskategoriForskning
Peer review utfördJa