{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:33:17Z","timestamp":1790911997354,"version":"4.1.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:p>The anorexic agent fenfluramine considerably increases the risk of primary pulmonary hypertension. The mechanism of this effect is unknown. The appetite-reducing action of fenfluramine is mediated by its interaction with the metabolism of serotonin [5-hydroxytryptamine (5-HT)] in the brain. We tested the hypothesis that the pulmonary vasoconstrictive action of fenfluramine is at least in part mediated by 5-HT receptor activation. In addition, we sought to determine whether pharmacological reduction of voltage-gated potassium (K<jats:sub>V<\/jats:sub>) channel activity would potentiate the pulmonary vascular reactivity to fenfluramine. Using isolated rat lungs perfused with Krebs-albumin solution, we compared the inhibitory effect of ritanserin, an antagonist of 5-HT<jats:sub>2<\/jats:sub>receptors, on fenfluramine- and 5-HT-induced vasoconstriction. Both 5-HT (10<jats:sup>\u22125<\/jats:sup>mol\/l) and fenfluramine (5 \u00d7 10<jats:sup>\u22124<\/jats:sup>mol\/l) caused significant increases in perfusion pressure. Ritanserin at a dose (10<jats:sup>\u22127<\/jats:sup>mol\/l) sufficient to inhibit &gt;80% of the response to 5-HT reduced the response to fenfluramine by \u223c50%. A higher ritanserin dose (10<jats:sup>\u22125<\/jats:sup>mol\/l) completely abolished the responses to 5-HT but had no more inhibitory effect on the responses to fenfluramine. A pharmacological blockade of K<jats:sub>V<\/jats:sub>channels by 4-aminopyridine (3 \u00d7 10<jats:sup>\u22123<\/jats:sup>mol\/l) markedly potentiated the pulmonary vasoconstrictor response to fenfluramine but was without effect on the reactivity to 5-HT. These data indicate that the pulmonary vasoconstrictor response to fenfluramine is partly mediated by 5-HT receptors. Furthermore, the pulmonary vasoconstrictor potency of fenfluramine is elevated when the K<jats:sub>V<\/jats:sub>-channel activity is low. This finding suggests that preexisting K<jats:sub>V<\/jats:sub>-channel insufficiency may predispose some patients to the development of pulmonary hypertension during fenfluramine treatment.<\/jats:p>","DOI":"10.1152\/jappl.2001.91.2.755","type":"journal-article","created":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T21:19:41Z","timestamp":1513977581000},"page":"755-761","source":"Crossref","is-referenced-by-count":28,"title":["Fenfluramine-induced pulmonary vasoconstriction: role of serotonin receptors and potassium channels"],"prefix":"10.1152","volume":"91","author":[{"given":"Simona","family":"B\u011blohl\u00e1vkov\u00e1","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Charles University First Medical School, Prague 128 53; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"\u0160im\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Charles University First Medical School, Prague 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