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Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions
W Auch-Schwelk1, Z S Katusic, P M Vanhoutte
1Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
Hypertension (Dallas, Tex. : 1979)
|June 1, 1990
Summary
Contractions in spontaneously hypertensive rat aortas involve thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors. Both acetylcholine and oxygen radicals trigger these contractions, suggesting PGH2 mediation and TXA2/PGH2 receptor activation.
Area of Science:
- Cardiovascular Physiology
- Vascular Pharmacology
- Biochemical Pathways
Background:
- Endothelium-dependent and independent contractions in spontaneously hypertensive rat (SHR) aortas are mediated by cyclooxygenase products.
- The specific role of thromboxane A2 (TXA2) or prostaglandin H2 (PGH2) in these contractions remains unidentified.
Purpose of the Study:
- To elucidate the involvement of TXA2 or PGH2 in endothelium-dependent contractions to acetylcholine and endothelium-independent contractions to oxygen-derived free radicals in SHR aortas.
- To investigate the role of TXA2/PGH2 receptors in mediating these vascular responses.
Main Methods:
- Isometric force measurements were performed on isolated thoracic aortic rings from SHR.
- Vascular contractions were induced by acetylcholine and oxygen-derived free radicals (xanthine/xanthine oxidase).
- The effects of a thromboxane synthetase inhibitor (dazoxiben) and TXA2/PGH2 receptor antagonists (AH 23,848, SQ 29,548, R 68,070) were evaluated.
Main Results:
- Acetylcholine induced endothelium-dependent contractions in SHR aortas.
- Oxygen-derived free radicals caused contractions in endothelium-denuded aortic rings.
- TXA2/PGH2 receptor antagonists significantly inhibited contractions to U 46,619, acetylcholine, and oxygen-derived free radicals.
- Dazoxiben did not affect acetylcholine-induced contractions.
- Acetylcholine stimulated prostacyclin release, but not TXA2, from SHR and WKY aortas.
Conclusions:
- Endothelium-dependent contractions in SHR aortas appear to be mediated by the stimulation of TXA2/PGH2 receptors, potentially by PGH2.
- Oxygen-derived free radicals may act as endothelium-derived contracting factors, ultimately causing contraction through TXA2/PGH2 receptor activation.