Fingolimod (FTY720) induces nitric oxide-dependent relaxation in the rat inferior vena cava via S1P3 receptor activation
Authors/Creators
- 1. Department of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo
- 2. Cardiovascular Surgery Clinic, University Clinical Center of Kosovo, Prishtina, Kosovo
- 3. Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", Università degli Studi di Milano, Milan, Italy|Department of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo
Description
Background: Sphingosine-1-phosphate (S1P) regulates vascular tone through multiple receptor subtypes. Although fingolimod (FTY720) has well-established effects in arterial systems, its effects on venous function remain poorly characterized.
Objective: This study aimed to investigate the direct effects of FTY720 on venous tone, with particular emphasis on vasorelaxation in the rat inferior vena cava, and to determine the involvement of S1P3 receptor-mediated nitric oxide (NO) signaling.
Methods: Isolated endothelium-intact rat inferior vena cava rings were mounted in organ baths for isometric tension recording. Vessels were precontracted with endothelin-1 (1 nM), followed by cumulative administration of FTY720 (1–30 µM). Mechanistic pathways were assessed using L-NAME, ODQ, and the S1P3 antagonist CAY10444.
Results: FTY720 induced concentration-dependent relaxation (Emax 63.9 ± 5.1%, p < 0.001). Inhibition of nitric oxide synthase and soluble guanylate cyclase significantly reduced relaxation, indicating involvement of the NO–cyclic guanosine monophosphate (cGMP) pathway. S1P3 receptor blockade nearly abolished the response, confirming receptor-specific signaling.
Conclusion: FTY720 induces significant venorelaxation and modulates venous tone in the rat inferior vena cava through an S1P3-dependent mechanism involving NO and cGMP signaling. These findings extend the vascular profile of FTY720 to the venous system, highlighting a key pathway in regulating venous tone.
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References
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