Thromboxane A2receptor antagonists inhibit endothelium-dependent contractions

Wolfgang Auch-Schwelk, Zvonimir S. Katusic, Paul M. Vanhoutte

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

Endothelium-dependent contractions to acetylcholine and endothelium-independent contractions to oxygen-derived free radicals in the aorta of the spontaneously hypertensive rat (SHR) are mediated by an unidentified product of the cyclooxygenase pathway of arachldonic acid metabolism. To determine the role of thromboxane A2(TXA2) or prostaglandin H2(PGH2) in these contractions, rings of the thoracic aorta of SHR were suspended in organ chambers for measurement of isometric force. Acetylcholine caused endothelium-dependent contractions in quiescent rings from SHR aortas. Oxygen-derived free radicals generated with xanthine plus xanthine oxidase caused contractions in rings without endothelium. Dazoxiben (thromboxane synthetase inhibitor) did not affect contractions evoked by acetylcholine. AH 23, 848, SQ 29, 548, or R 68, 070 (TXA2/PGH2receptor antagonists) inhibited contractions to U 46, 619 (a TXA2/PGH2receptor agonist), acetylcholine, and oxygen-derived free radicals. Acetylcholine stimulated the release of prostacyclin from Wistar-Kyoto (WKY) rat and SHR aortas but not the release of other prostaglandins (PGE2, PGF, TXA2). Oxygen-derived free radicals did not stimulate the release of prostaglandins from either SHR or WKY rat aortas. These results demonstrate that stimulation of TXA2/PGH2receptors probably by PGH2might be involved in endothelium-dependent contractions. Oxygen-derived free radicals, which might be an endothelium-derived contracting factor or factors, ultimately cause contraction by stimulation of TXA2/PGH2receptors.

Original languageEnglish (US)
Pages (from-to)699-703
Number of pages5
JournalHypertension
Volume15
Issue number6
DOIs
StatePublished - Jun 1990

Keywords

  • Acetylcholine
  • Endothelium
  • Prostaglandins
  • Spontaneously hypertensive rats
  • Thromboxane

ASJC Scopus subject areas

  • Internal Medicine

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