Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction

Tereza Cristina Buzinari; Jorge Camargo Oishi; Thiago Francisco De Moraes; Izabela Pereira Vatanabe; Heloisa Sobreiro Selistre-de-Araújo; Cezar Rangel Pestana; Gerson Jhonatan Rodrigues

doi:10.1016/j.ejps.2017.04.022

Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction

Eur J Pharm Sci. 2017 Jul 15:105:144-149. doi: 10.1016/j.ejps.2017.04.022. Epub 2017 Apr 27.

Authors

Tereza Cristina Buzinari¹, Jorge Camargo Oishi¹, Thiago Francisco De Moraes¹, Izabela Pereira Vatanabe¹, Heloisa Sobreiro Selistre-de-Araújo¹, Cezar Rangel Pestana², Gerson Jhonatan Rodrigues³

Affiliations

¹ Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
² Instituto Latino Americano de Ciências da Vida e Natureza (ILACVN), Universidade Federal da Integração Latino-Americana, Foz do Iguaçu, PR, Brazil.
³ Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP, Brazil. Electronic address: gerson@ufscar.br.

PMID: 28456572
DOI: 10.1016/j.ejps.2017.04.022

Abstract

Purpose: Verify if sodium nitroprusside (SNP) is able to improve endothelial function and if this effect is independent of nitric oxide (NO) release of the compound.

Methods: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact endothelium aortas were placed in a myograph and incubated with SNP: 0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0.1nM or DETA/NO 0.1μM. The detection of intracellular superoxide radical (O₂^•-) was obtained by using DHE probe.

Results: Treatment of 2K-1C aortic rings with SNP (0.1; 1.0 and 10nM) improved endothelium dependent relaxation induced by acetylcholine. This improvement induced by SNP was verified at the concentration of 0.1nM, which does not release NO, suggesting that this effect was not induced due to NO release by SNP compound. Besides, we show that the cell treatment with 0.1nM of SNP decreased the fluorescence intensity to DHE in cells stimulated with angiotensin II. These results indicate that SNP decreases the concentration of O₂^•- in HUVEC cells.

Conclusions: The SNP at a concentration that does not release NO inside the cells is able to attenuate endothelial dysfunction.

Drugs and chemicals: Acetylcholine (Ach) (PubChem CID:6060); angiotensin II human (Ang II) (PubChem CID: 16211177); diethylenetriamine/nitric oxide (DETA-NO) (PubChem CID 4518); dihydroethidium (DHE) (PubChem CID: 128682); phenylephrine (Phe) (PubChem CID: 5284443); sodium nitroprusside (SNP) (PubChem CID: 11963579); Thiazolyl Blue Tetrazolium Bromide (MTT) (PubChem CID: 64965); 4,5-diaminofluorescein diacetate (DAF-2DA); 4-hidroxy-Tempo (Tempol) (PubChem CID: 137994), were purchased from Sigma-Aldrich (St. Louis, MO, USA).

Keywords: Endothelial dysfunction; Nitric oxide; Sodium nitroprusside; Superoxide.

MeSH terms

Animals
Antihypertensive Agents / pharmacology*
Aorta, Thoracic / drug effects*
Aorta, Thoracic / physiology
Cell Survival / drug effects
Cells, Cultured
Human Umbilical Vein Endothelial Cells / drug effects
Human Umbilical Vein Endothelial Cells / metabolism
Humans
Hypertension, Renovascular / metabolism
Hypertension, Renovascular / physiopathology
In Vitro Techniques
Male
Nitric Oxide / metabolism
Nitric Oxide Donors / pharmacology*
Nitroprusside / pharmacology*
Rats, Wistar
Superoxides / metabolism
Vasodilator Agents / pharmacology*

Substances

Antihypertensive Agents
Nitric Oxide Donors
Vasodilator Agents
Superoxides
Nitroprusside
Nitric Oxide