Cardiovascular remodeling and the peripheral serotonergic system.

Area of Science:

• Cardiovascular Pharmacology
• Neuroscience
• Drug Discovery

Background:

• Plasma 5-hydroxytryptamine (5-HT; serotonin), released from blood platelets, significantly impacts the human cardiovascular system.
• Numerous widely used medications targeting serotonergic receptors may increase cardiovascular risk.
• Serotonin receptor activation can elicit both acute and chronic cardiovascular effects.

Purpose of the Study:

• To review the acute and chronic cardiovascular side effects associated with serotonin receptor activation.
• To explore the role of serotonin and its receptors in cardiovascular tissue remodeling, including cardiac hypertrophy, fibrosis, and valve degeneration.
• To discuss the pharmacology of the 5-HT2A receptor in vasomotor tone regulation and its interaction with endothelial and smooth muscle cells, using sarpogrelate as an example.

Main Methods:

• Literature review focusing on the cardiovascular effects of serotonin and its receptor subtypes.
• Analysis of acute responses, including the Bezold-Jarish reflex, involving specific 5-HT receptors (5-HT3, 5-HT1B/1D, 5-HT7, 5-HT2A/2B).
• Exploration of chronic effects on cardiovascular remodeling mediated by 5-HT4 and 5-HT2A/2B receptors.

Main Results:

• The Bezold-Jarish reflex, triggered by acute 5-HT exposure, causes bradycardia and atrioventricular block via specific serotonin receptors.
• Chronic activation of 5-HT receptors contributes to cardiac hypertrophy, fibrosis, and valve degeneration.
• 5-HT2A receptor activity influences vasomotor tone and endothelial-smooth muscle cell interactions.

Conclusions:

• Serotonin receptor activation presents significant acute and chronic risks to cardiovascular health.
• Understanding these mechanisms is crucial for developing targeted therapies to prevent serotonin-induced cardiac side effects.
• Further research into 5-HT receptor pharmacology may lead to novel preventative strategies.