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The vasorelaxant effects of 1-nitro-2-phenylethane involve stimulation of the soluble guanylate cyclase-cGMP pathway
- Source :
- Biochemical Pharmacology. 85:780-788
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- 1-Nitro-2-phenylethane is the first organic NO2-containing molecule isolated from plants. It possesses interesting hypotensive, bradycardic, and vasodilator properties, but the mode by which it induces vasorelaxation is still unknown. The underlying mechanism involved in the vasodilator effect of 1-nitro-2-phenylethane was investigated in rat aorta. The vasorelaxant effects of 1-nitro-2-phenylethane did not depend on endothelial layer integrity, and the effects were refractory to L-NG-nitroarginine methyl ester (L-NAME)-induced nitric oxide synthase inhibition. Vasorelaxation was similarly resistant to treatment with indomethacin, cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL-12330A), and KT5720, indicating that neither prostaglandin release nor adenylyl cyclase activation is involved. Conversely, methylene blue- and ODQ-induced guanylate cyclase inhibition reduced the vasorelaxation induced by 1-nitro-2-phenylethane. The pharmacological blockade of K+ channels with tetraethylammonium, glybenclamide, and 4-aminopyridine also blunted vasorelaxation induced by 1-nitro-2-phenylethane. The effects of 1-nitro-2-phenylethane were reversed by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and comparable to the effects induced by sodium nitroprusside. In silico analysis using an Ns H-NOX subunit of guanylate cyclase revealed a pocket on the macromolecule surface where 1-nitro-2-phenylethane preferentially docked. In vitro, 1-nitro-2-phenylethane increased cyclic guanosine 3′,5′-monophosphate (cGMP) levels in rat aortic rings, an effect also reversed by ODQ. In conclusion, 1-nitro-2-phenylethane produces vasodilator effects by stimulating the soluble guanylate cyclase-cGMP pathway.
- Subjects :
- Male
GUCY1B3
medicine.medical_specialty
Vasodilator Agents
Receptors, Cytoplasmic and Nuclear
Prostaglandin
Guanosine
Pharmacology
Biochemistry
Guanylate cyclase stimulation
chemistry.chemical_compound
Soluble Guanylyl Cyclase
Internal medicine
Benzene Derivatives
medicine
Animals
Rats, Wistar
Cyclic GMP
Tetraethylammonium
biology
Chemistry
GUCY1A3
Nitroderivative
Rats
Nitric oxide synthase
Endocrinology
Guanylate Cyclase
biology.protein
Sodium nitroprusside
Soluble guanylyl cyclase
medicine.drug
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 85
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....eb228b6922ce71f53c652472ed8763be