PMID: 9525298Apr 3, 1998Paper

Thromboxane inhibition and monocrotaline-induced pulmonary hypertension in rats

Respirology : Official Journal of the Asian Pacific Society of Respirology
T NagataM Omata

Abstract

Monocrotaline (MCT)-induced pulmonary hypertension (PH) is a useful model for the investigation of this disorder in humans. The role of thrombocytes in the genesis of PH has already been addressed; however, the exact mechanism by which they induce PH remains to be elucidated. We investigated the effects of a thromboxane A2 (TXA2) synthase inhibitor (OKY-046) and a TXA2/prostaglandin H2 (PGH2) receptor antagonist (ONO-8809) on the development of MCT-induced PH. A single dose of MCT (60 mg/kg bodyweight; BW) was injected subcutaneously in Wistar rats 24 h after the administration of OKY-046 or ONO-8809. The TXA2 inhibitors were administered by gavage daily for 3 weeks. Urinary excretion of eicosanoids was determined by radioimmunoassay. At the end of the treatment period, the lungs, heart and kidneys were morphologically examined. The per cent medial thickness of the muscular pulmonary arteries (%MT) and the ratio of the right to the left ventricular mass including the septum (RV/LV + S) increased significantly in MCT-treated rats compared with the control rats. The %MT was attenuated by the administration of ONO-8809. Either OKY-046 or ONO-8809 attenuated the increase in RV/LV + S. In addition, both TXA2 inhibitors reduced urina...Continue Reading

References

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Citations

Mar 24, 2004·Chemistry and Physics of Lipids·L J Janssen
Jan 15, 2005·Antioxidants & Redox Signaling·Luke J JanssenPeter Helli
Nov 3, 2007·American Journal of Respiratory and Critical Care Medicine·Hiroaki ObataNoritoshi Nagaya
Apr 29, 2008·American Journal of Respiratory Cell and Molecular Biology·Luke J Janssen
Aug 10, 2000·Pulmonary Pharmacology & Therapeutics·L J Janssen
Jun 22, 2014·Circulation Research·Roxane Paulin, Evangelos D Michelakis
May 15, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·L J Janssen

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