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Sertraline Causes Strong Coronary Vasodilation: Possible Relevance for Cardioprotection by Selective Serotonin Reuptake Inhibitors

  • Basic Pharmacology
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Summary

Objective: Although Selective Serotonin Reuptake Inhibitors (SSRIs) are important antidepressant drugs, knowledge of their vaso active effects is limited. Vaso active effects of the SSRI sertraline were studied in rings of rat aorta, human Internal Mammary Arteries (IMAs) and in Langendorff perfused rat hearts.

Methods: The effects of sertraline (0.1 to 300 μ mol ⋅ L− 1) on precontracted rat aortic and IMA rings were evaluated in organ bath chambers. Precontraction was elicited by serotonin (5-HT; 10 μ mol ⋅ L− 1), phenylephrine (PE; 10 μ mol ⋅ L− 1) and potassium chloride (KCl; 50 mmol ⋅ L− 1). In addition, the effects of sertraline on PE induced contraction curves were established by subjecting vascular rings to increasing doses of PE (1 nmol ⋅ L− 1 to 10 μ mol ⋅ L− 1) in the presence of sertraline or vehicle. Finally, the effects of sertraline on ex vivo coronary flow in rat hearts were examined using a retrograde Langendorff perfusion model.

Results: Sertraline elicited dose-dependent relaxation, independent of the substance used for precontraction (p < 0.025). Sertraline showed a rightward shift of dose-response curves to PE (p < 0.01). Vasodilatory effects of SSRIs were endothelium independent. In perfused rat hearts, sertraline (0.3 to 10 μ mol ⋅ L− 1) showed a concentration-dependent increase in coronary flow that returned to baseline levels after wash-out of the antidepressant (p = 0.005).

Conclusions: One of the SSRIs, sertraline, showed marked vasodilatory effects in rat aorta and human IMAs. Sertraline elicited vasodilatation in coronary arteries during perfusion of rat hearts. These hemodynamic effects may explain the observed beneficial effects in myocardial ischemia and infarction.

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Authors and Affiliations

  1. Thorax Center, Departments of Cardiology, University Hospital Groningen, POB 30.001, Groningen, The Netherlands

    Joost P. van Melle MD, Maarten P. van den Berg & Dirk J. van Veldhuisen

  2. Department of Clinical Pharmacology, University of Groningen, Groningen, POB 30.001, The Netherlands

    Hendrik Buikema, Azuwerus van Buiten & Wiek H. van Gilst

  3. Thorax Center, Departments of Thoracic Surgery, University Hospital Groningen, POB 30.001, Groningen, The Netherlands

    Piet W. Boonstra

  4. Department of Cardiology, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700, RB Groningen, The Netherlands

    Joost P. van Melle MD

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  1. Joost P. van Melle MD
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  2. Hendrik Buikema
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Correspondence to Joost P. van Melle MD.

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van Melle, J.P., Buikema, H., van den Berg, M.P. et al. Sertraline Causes Strong Coronary Vasodilation: Possible Relevance for Cardioprotection by Selective Serotonin Reuptake Inhibitors. Cardiovasc Drugs Ther 18, 441–447 (2004). https://doi.org/10.1007/s10557-004-6221-3

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