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Serotonin aggravates exercise-induced cardiac ischemia in the dog: effect of serotonin receptor antagonists
Ist Teil von
European journal of pharmacology, 2004-08, Vol.497 (1), p.55-63
Ort / Verlag
Amsterdam: Elsevier B.V
Erscheinungsjahr
2004
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
We investigated the effects of serotonin (5-HT), SL65.0472 (7-fluoro-2-oxo-4-[2-[4-thieno[3,2-
c]pyridine-4-yl)piperazin-1-yl]ethyl]-1,2-dihydroquinoline-1-acetamide, a 5-HT
1B/5-HT
2A receptor antagonist) and ketanserin (a 5-HT
2A receptor antagonist) during exercise-induced cardiac ischemia in conscious dogs. Dogs were administered a hypercholesterolemic diet and an inhibitor of nitric oxide synthetase to produce chronic endothelial dysfunction. Myocardial ischemia was induced by a treadmill exercise test associated with limitation of left anterior descending coronary blood flow. Infusion of serotonin during exercise produced dose-related cardiovascular changes (after 10 μg/kg/min; heart rate +27±6 bpm, systolic blood pressure +18±3 mm Hg, left circumflex coronary blood flow +64±8 ml/min, myocardial segment length shortening in the ischemic zone −5.9±1.9%,
P<0.05). SL65.0472 blocked serotonin-induced increases in blood pressure, rate pressure product and circumflex coronary artery flow (100 μg/kg i.v.,
P<0.05) and reduced serotonin-induced ischemic myocardial segment length shortening (300 μg/kg i.v.,
P<0.05). Ketanserin (30–300 μg/kg i.v.) had no significant effect on any serotonin-induced changes during exercise. Thus, SL65.0472 opposes serotonin-induced myocardial dysfunction in a dog model of exercise-induced ischemia.