Sertraline causes strong coronary vasodilation: possible relevance for cardioprotection by selective serotonin reuptake inhibitors.
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 micromol x L(-1)) on precontracted rat aortic and IMA rings were evaluated in organ bath chambers. Precontraction was elicited by serotonin (5-HT; 10 micromol x L(-1)), phenylephrine (PE; 10 micromol x L(-1)) and potassium chloride (KCl; 50 mmol x 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 x L(-1) to 10 (micro)mol x 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 micromol x 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
van Melle
Joost P
JP
Thorax Center, Departments of Cardiology, University Hospital Groningen, POB 30.001 Groningen, The Netherlands. j.p.van.melle@med.rug.nl
Buikema
Hendrik
H
van den Berg
Maarten P
MP
van Buiten
Azuwerus
A
van Veldhuisen
Dirk J
DJ
Boonstra
Piet W
PW
van Gilst
Wiek H
WH
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000473:pathology; D009131:Muscle, Smooth, Vascular; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020280:Sertraline / Q000494:pharmacology / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline