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Serotonin regulates the cardiopulmonary effects of pulmonary embolism through vagal C‐fiber activation
Author(s) -
Chou Yangling,
Canning Brendan James
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1077.2
Subject(s) - ketanserin , anesthesia , tachypnea , medicine , serotonin , platelet activation , endocrinology , 5 ht receptor , pharmacology , tachycardia , platelet , receptor
We have addressed the hypothesis that the tachypnea, tachycardia and pulmonary hypertension evoked by pulmonary embolism (PE) occur secondary to platelet activation/degranulation followed by serotonin‐dependent pulmonary C‐fiber activation. In anesthetized guinea pigs, intravenously administered equine collagen induced immediate, sustained (>20 minutes) and pronounced (~200%) increases in respiratory rate, transient falls in blood pressure and sustained increases in right ventricular pressure (n=10). These effects were mimicked by 5‐HT and the P2Y receptor agonist and platelet stimulant ADP (n=5/treatment group), and prevented by prior platelet depletion (>90% reduction) with busulfan (n=5). The serotonin reuptake inhibitor fluoxetine (1mg/kg iv) rendered ADP challenges lethal (n=5). Vagotomy prevented the tachypnea and systemic hypotension evoked by PE (n=4). The 5‐HT3 receptor antagonist ondansetron (1 mg/kg iv) nearly abolished the responses to 5‐HT and prevented the lethal effects of ADP challenge following fluoxetine (n=5/treatment group). Ondansetron also markedly attenuated the tachypnea and hypotension accompanying PE (n=8). Based on these results we speculate that the cardiopulmonary reflexes evoked by PE depend upon platelet serotonin release and subsequent activation of pulmonary C‐fibers via 5‐HT3 receptors.