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Sertraline causes strong coronary vasodilation: Possible relevance for cardioprotection by selective serotonin reuptake inhibitors

van Melle, JP., Buikema, H., van den Berg, MP., van Buiten, A., van Veldhuisen, DJ., Boonstra, PW. & van Gilst, WH., Nov-2004, In : Cardiovascular Drugs and Therapy. 18, 6, p. 441-447 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

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 mu mol center dot L-1) on precontracted rat aortic and IMA rings were evaluated in organ bath chambers. Precontraction was elicited by serotonin (5-HT; 10 mu mol center dot L-1), phenylephrine ( PE; 10 mu mol center dot L-1) and potassium chloride (KCl; 50 mmol center dot 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 center dot L-1 to 10 mu mol center dot 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 mu mol center dot 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.

Original languageEnglish
Pages (from-to)441-447
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume18
Issue number6
Publication statusPublished - Nov-2004

    Keywords

  • 5-HT (5-hydroxytryptamine, serotonin), pharmacology, smooth muscle relaxation, vasodilation, sertraline, SSRI, MYOCARDIAL-INFARCTION, MAJOR DEPRESSION, BYPASS-SURGERY, SMOOTH-MUSCLE, DOUBLE-BLIND, FLUOXETINE, ARTERIES, ANTIDEPRESSANTS, 5-HYDROXYTRYPTAMINE, CONTRACTION

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