Role of serotonin in thromboxane A2-induced coronary chemoreflex.
We reported previously that the thromboxane A(2) (TxA(2)) mimetic U-46619 stimulates cardiac vagal afferent nerves, eliciting a reflex decrease in heart rate (HR) and arterial blood pressure (ABP). The present experiments were designed to test the hypothesis that TxA(2) evokes these changes via the release of serotonin [5-hydroxytryptamine (5-HT)] and activation of the 5-HT(3) receptor. Injections of the 5-HT(3) antagonist tropisetron (1 mg of 3-tropanyl-indole-3-carboxylate or ICS-205-930) attenuated the decreases in HR and ABP induced by left atrial injections of U-46619 (20 microg). Tropisetron administration also eliminated the U-46619-induced increase in impulse frequency in a majority of cardiac, vagal afferent units tested. Measurement of serum 5-HT levels revealed an elevation in serum 5-HT levels after U-46619 injection in those rabbits that displayed a significant HR change following injection of U-46619. These results indicate that although other factors may also contribute to these reflex responses, the release of 5-HT and stimulation of the 5-HT(3) receptor plays a significant role in coronary reflexes induced by TxA(2).
Wacker
M J
MJ
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA. mjwacker@ku.edu
Wilhelm
H L
HL
Gomez
S E
SE
Floor
E
E
Orr
J A
JA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology*; D004333:Drug Administration Routes; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D012701:Serotonin / Q000097:blood / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013928:Thromboxane A2 / Q000502:physiology*; D000077526:Tropisetron; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007211:Indoles; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; D012701:Serotonin; D013928:Thromboxane A2; D000077526:Tropisetron; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid