Serotonergic Modulation of Cardiovascular Function

Serotonin (5-hydroxytryptamine, 5-HT) exerts multifaceted control over cardiovascular homeostasis through central and peripheral mechanisms. In the central nervous system, distinct 5-HT receptor subtypes modulate autonomic outflow, influencing heart rate and vascular tone. Peripherally, 5-HT can act directly on vascular smooth muscle or endothelium to induce vasoconstriction or vasodilation, depending on receptor distribution and local signalling pathways. Prejunctional 5-HT receptors on sympathetic and sensory nerves fine-tune neurotransmitter release, altering noradrenaline and neuropeptide output to adjust blood pressure. Key receptor families include the inhibitory 5-HT1 and excitatory 5-HT2 metabotropic receptors, as well as the ligand-gated 5-HT3 ion channel. The 5-HT7 subtype has emerged as a major mediator of hypotension via cyclic AMP-dependent relaxation of skeletal muscle and splanchnic vessels. Nitric oxide (NO) often underlies 5-HT-induced vasorelaxation, whereas thromboxane A2 or calcium influx may drive constrictive responses. Altered serotonergic control contributes to hypertension, diabetic cardiovascular complications and the vascular side effects of selective serotonin reuptake inhibitors. Understanding receptor-specific actions of 5-HT offers therapeutic potential for fine-tuning vascular resistance and autonomic balance in disease states.

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Research from all publishers

Recent studies have illuminated peripheral 5-HT1D receptor function in diabetic renal vasculature. In alloxan-treated rats, enhanced renal sympathetic responses were tempered by activation of prejunctional 5-HT1D receptors engaging a guanylyl cyclase-NO pathway, revealing a mechanism to offset diabetes-induced vasopressor hyperactivity. A comprehensive review of neurovascular transmission has mapped the array of prejunctional 5-HT receptors on autonomic and sensory perivascular nerves, showing that receptor-specific facilitation or inhibition of noradrenaline, acetylcholine and calcitonin gene-related peptide release can yield opposing effects on blood pressure regulation. Another investigation into cutaneous circulation during 5-HT infusion demonstrated that hypotension arises in part from reduced skin vascular resistance, independent of active hyperaemia, highlighting the cutaneous bed’s contribution to total peripheral resistance. Together, these insights underscore the diversity of 5-HT receptor pathways in controlling vascular beds and the therapeutic relevance of targeting specific subtypes to modulate blood pressure and organ perfusion.

Serotonergic Modulation of Cardiovascular Function publication trend

The graph below shows the total number of articles in serotonergic modulation of cardiovascular function across all publications each year (not limited to Nature Index journals).

Technical terms

5-HT (serotonin): Monoamine neurotransmitter that acts centrally and peripherally to regulate heart rate and vessel tone.

Prejunctional receptor: Receptor on nerve terminals that influences release of neurotransmitters affecting vascular function.

Postjunctional receptor: Receptor on vascular smooth muscle or endothelium that mediates direct changes in vessel contraction or relaxation.

Vascular resistance: Opposition to blood flow determined by vessel diameter, tone and blood viscosity.

Endothelium: Inner lining of blood vessels that secretes factors such as nitric oxide to modulate vascular tone.

Nitric oxide (NO): Endothelium-derived gas that induces smooth muscle relaxation and vasodilation.

References

1. Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway. International Journal of Molecular Sciences (2023).
2. Serotonergic Modulation of Neurovascular Transmission: A Focus on Prejunctional 5-HT Receptors/Mechanisms. Biomedicines (2023).
3. Skin Vascular Resistance Decreases during 5-HT-Induced Hypotension in the Rat. Biomedicines (2023).
4. Reduction in Hindquarter Vascular Resistance Supports 5-HT7 Receptor Mediated Hypotension. Frontiers in Physiology (2021).
5. Contribution of Thromboxane A2 in Rat Common Carotid Artery Response to Serotonin. Scientia Pharmaceutica (2010).
6. Potential Adverse Cardiovascular Effects of Treatment With Fluoxetine and Other Selective Serotonin Reuptake Inhibitors (SSRIs) in Patients With Geriatric Depression: Implications for Atherogenesis and Cerebromicrovascular Dysregulation. Frontiers in Genetics (2019).