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Inflammopharmacology

Erschienen in:

10.04.2023 | Original Article

New insights on mode of action of vasorelaxant activity of simvastatin

verfasst von: Kanika Verma, Rahul Shukla, Jaya Dwivedi, Sarvesh Paliwal, Swapnil Sharma

Erschienen in: Inflammopharmacology | Ausgabe 3/2023

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Abstract

Simvastatin is a semisynthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and is used extensively to treat atherosclerotic cardiovascular disease. Apart from the lipid-lowering effect, simvastatin has been documented to offer impressive vasorelaxant activity. However, the mechanism associated with this vasorelaxant activity has yet not been substantially explored. Thus, the present study has aimed to elucidate the mechanism(s) associated with simvastatin-induced vasorelaxation using an established rat aortic ring model. The results from the study depicted that simvastatin caused significant relaxation in aortic rings pre-contracted with phenylephrine and potassium chloride (KCl). The vasorelaxant effect of simvastatin was attenuated by methylene blue (sGC-dependent cyclic guanosine monophosphate (cGMP) inhibitor), N^G-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor), 4-aminopyridine (K_v blocker), glibenclamide (K_ATP blocker), and barium chloride (K_ir blocker). In addition, the vasorelaxant effect of simvastatin was slightly reduced by PD123319 (angiotensin II type 2 receptor (AT₂R) antagonist). However, indomethacin (COX inhibitor), 1H-[1,2,4]Ox adiazolol [4,3-α]quinoxalin-1-one (ODQ; selective soluble guanylate cyclase (sGC) inhibitor), losartan (angiotensin II type 1 receptor (AT₁R) antagonist), atropine (muscarinic receptor blocker), and tetraethyl ammonium (TEA; K_Ca blocker) did not affect the vasorelaxant effect of simvastatin. Furthermore, simvastatin was found to attenuate the release of calcium (Ca²⁺) from intracellular stores in the presence of ruthenium red (ryanodine receptor, RyR inhibitor) and extracellular stores via nifedipine (voltage-operated Ca²⁺ channels, VOCC blocker) and SK&F96365 (receptor-operated Ca²⁺ channel, ROCC blocker). Thus, it can be concluded that the vasorelaxant effect of simvastatin involves NO/cGMP pathways, AT₂R receptors, Ca²⁺ channels, and K⁺ channels.

Graphical abstract

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Titel: New insights on mode of action of vasorelaxant activity of simvastatin
verfasst von: Kanika Verma
Rahul Shukla
Jaya Dwivedi
Sarvesh Paliwal
Swapnil Sharma
Publikationsdatum: 10.04.2023
Verlag: Springer International Publishing
Erschienen in: Inflammopharmacology / Ausgabe 3/2023
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-023-01219-8

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

New insights on mode of action of vasorelaxant activity of simvastatin

Abstract

Graphical abstract

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Graphical abstract

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