Cell Biochemistry and Biophysics

, Volume 61, Issue 1, pp 23–31 | Cite as

Aspirin Attenuates Pulmonary Arterial Hypertension in Rats by Reducing Plasma 5-Hydroxytryptamine Levels

  • Lan Shen
  • Jieyan Shen
  • Jun Pu
  • Ben He
Original Paper


Pulmonary arterial hypertension (PAH) is characterized by increasing pulmonary pressure, right ventricular failure, and death. The typical pathological changes include medial hypertrophy, intimal fibrosis and in situ thrombosis. Serotonin (5-HT) and other factors contribute to the development of pathologic lesions. Aspirin (ASA), a platelet aggregation inhibitor, inhibits 5-HT release from platelets. The aim of this study was to determine the efficacy of ASA in preventing or attenuating PAH. Sprague–Dawley rats injected with monocrotaline (MCT) developed severe PAH within 31 days. One hundred forty rats were randomized to receive either vehicle or ASA (0.5, 1, 2, or 4 mg/kg/day). The pre-ASA group was treated with ASA (1 mg/kg/day) for 30 days before the MCT injection. Thirty-one days after the injection (day 61 for the pre-ASA group), pulmonary arterial pressure (PAP), right ventricular hypertrophy and pulmonary arteriole thickness were measured. Plasma 5-HT was measured by high-performance liquid chromatography. Aspirin suppressed PAH and increased the survival rate compared with the control group (84 vs. 60%, P < 0.05). Aspirin treatment also reduced right ventricular hypertrophy and pulmonary arteriole proliferation in ASA-treated PAH model. In addition, plasma 5-HT was decreased in our ASA-treated PAH model. The degree of 5-HT reduction was associated with systolic PAP, right ventricular hypertrophy and wall thickness of pulmonary arterioles in rats. These results showed that ASA treatment effectively attenuated MCT-induced pulmonary hypertension, right ventricular hypertrophy, and occlusion of the pulmonary arteries. The effects of ASA was associated with a reduction of 5-HT.


Pulmonary arterial hypertension Aspirin Monocrotaline 5-HT 





Idiopathic pulmonary arterial hypertension


High-performance liquid chromatography


Left ventricle




Mean pulmonary arterial pressure


Mean systemic arterial pressure


Pulmonary arterial hypertension


Pulmonary arterial smooth muscle cell




Right ventricle


Right ventricular hypertrophy index


Right ventricular systolic pressure




Serotonin reuptake transporter


Systolic pulmonary arterial pressure

WA %

Percent wall area



We thank Dr. Cai Yong for his help with statistics, Dr. Lin Peisen for help with the rat experiments and Mr. David Proctor for English revising. This study was supported by a grant from the Shanghai Municipal Health Bureau (2007103).


  1. 1.
    Tuder, R. M., Marecki, J. C., Richter, A., et al. (2007). Pathology of pulmonary hypertension. Clinics in Chest Medicine, 28(1), 23–42, vii.PubMedCrossRefGoogle Scholar
  2. 2.
    Carlino, C., Tobias, J. D., Schneider, R. I., et al. (2010). Pulmonary hemodynamic response to acute combination and monotherapy with sildenafil and brain natriuretic peptide in rats with monocrotaline-induced pulmonary hypertension. American Journal of the Medical Sciences, 339(1), 55–59.PubMedCrossRefGoogle Scholar
  3. 3.
    Gurtner, H. P. (1985). Aminorex and pulmonary hypertension. A review. Cor et Vasa, 27(2–3), 160–171.PubMedGoogle Scholar
  4. 4.
    MacLean, M. R., Herve, P., Eddahibi, S., et al. (2000). 5-hydroxytryptamine and the pulmonary circulation: Receptors, transporters and relevance to pulmonary arterial hypertension. British Journal of Pharmacology, 131(2), 161–168.PubMedCrossRefGoogle Scholar
  5. 5.
    MacLean, M. R. (2007). Pulmonary hypertension and the serotonin hypothesis: Where are we now? International Journal of Clinical Practice Supplement, 156, 27–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Kanai, Y., Hori, S., Tanaka, T., et al. (1993). Role of 5-hydroxytryptamine in the progression of monocrotaline induced pulmonary hypertension in rats. Cardiovascular Research, 27(9), 1619–1623.PubMedCrossRefGoogle Scholar
  7. 7.
    Herve, P., Launay, J. M., Scrobohaci, M. L., et al. (1995). Increased plasma serotonin in primary pulmonary hypertension. American Journal of Medicine, 99(3), 249–254.PubMedCrossRefGoogle Scholar
  8. 8.
    Guignabert, C., Raffestin, B., Benferhat, R., et al. (2005). Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Circulation, 111(21), 2812–2819.PubMedCrossRefGoogle Scholar
  9. 9.
    Hironaka, E., Hongo, M., Sakai, A., et al. (2003). Serotonin receptor antagonist inhibits monocrotaline-induced pulmonary hypertension and prolongs survival in rats. Cardiovascular Research, 60(3), 692–699.PubMedCrossRefGoogle Scholar
  10. 10.
    Tsai, T. H., Tsai, W. J., & Chen, C. F. (1995). Aspirin inhibits collagen-induced platelet serotonin release, as measured by microbore high-performance liquid chromatography with electrochemical detection. Journal of Chromatography. B Biomedical Applications, 669(2), 404–407.CrossRefGoogle Scholar
  11. 11.
    De, C. F. (1990). The role of serotonin in thrombogenesis. Clinical Physiology and Biochemistry, 8(Suppl 3), 40–49.Google Scholar
  12. 12.
    Kentera, D., Susic, D., & Zdravkovic, M. (1979). Effects of verapamil and aspirin on experimental chronic hypoxic pulmonary hypertension and right ventricular hypertrophy in rats. Respiration, 37(4), 192–196.PubMedCrossRefGoogle Scholar
  13. 13.
    Delcroix, M., Melot, C., Lejeune, P., et al. (1992). Cyclooxygenase inhibition aggravates pulmonary hypertension and deteriorates gas exchange in canine pulmonary embolism. American Review of Respiratory Disease, 145(4 Pt 1), 806–810.PubMedGoogle Scholar
  14. 14.
    Schultze, A. E., & Roth, R. A. (1998). Chronic pulmonary hypertension—the monocrotaline model and involvement of the hemostatic system. Journal of Toxicology and Environmental Health Part B: Critical Reviews, 1(4), 271–346.CrossRefGoogle Scholar
  15. 15.
    Eddahibi, S., Humbert, M., Fadel, E., et al. (2001). Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. Journal of Clinical Investigation, 108(8), 1141–1150.PubMedGoogle Scholar
  16. 16.
    Guignabert, C., Izikki, M., Tu, L. I., et al. (2006). Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circulation Research, 98(10), 1323–1330.PubMedCrossRefGoogle Scholar
  17. 17.
    Morecroft, I., Pang, L., Baranowska, M., et al. (2010). In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension. Cardiovascular Research, 85(3), 593–603.PubMedCrossRefGoogle Scholar
  18. 18.
    Newman, J. H., Fanburg, B. L., Archer, S. L., et al. (2004). Pulmonary arterial hypertension: Future directions: Report of a National Heart, Lung and Blood Institute/Office of Rare Diseases workshop. Circulation, 109(24), 2947–2952.PubMedCrossRefGoogle Scholar
  19. 19.
    Dumitrascu, R., Koebrich, S., Dony, E., et al. (2008). Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury. BMC Pulmonary Medicine, 8, 25.PubMedCrossRefGoogle Scholar
  20. 20.
    Ramos, M. F., Lame, M. W., Segall, H. J., et al. (2008). Smad signaling in the rat model of monocrotaline pulmonary hypertension. Toxicologic Pathology, 36(2), 311–320.PubMedCrossRefGoogle Scholar
  21. 21.
    Vane, J. R., & Botting, R. M. (2003). The mechanism of action of aspirin. Thrombosis Research, 110(5–6), 255–258.PubMedCrossRefGoogle Scholar
  22. 22.
    Johnson, S. R., Granton, J. T., & Mehta, S. (2006). Thrombotic arteriopathy and anticoagulation in pulmonary hypertension. Chest, 130(2), 545–552.PubMedCrossRefGoogle Scholar
  23. 23.
    Shen, J., He, B., & Wang, B. (2005). Effects of lipo-prostaglandin E1 on pulmonary hemodynamics and clinical outcomes in patients with pulmonary arterial hypertension. Chest, 128(2), 714–719.PubMedCrossRefGoogle Scholar
  24. 24.
    Robbins, I. M., Kawut, S. M., Yung, D., et al. (2006). A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension. European Respiratory Journal, 27(3), 578–584.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Cardiovascular Department, Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina

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