Enhancement on reactive oxygen species and COX ‐1 m RNA levels modulate the vascular relaxation induced by sodium nitroprusside in denuded mice aorta
This study aimed to investigate the modulation of nitric oxide/reactive oxygen species in sodium nitroprusside relaxation in mice aorta. Sodium nitroprusside induced relaxation in endothelium‐intact (e+) and endothelium‐denuded (e−) aortas with greater potency in e+ than in e−. The nitric oxide synt...
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Veröffentlicht in: | Fundamental & clinical pharmacology 2015-04, Vol.29 (2), p.150-163 |
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Sprache: | eng |
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Zusammenfassung: | This study aimed to investigate the modulation of nitric oxide/reactive oxygen species in sodium nitroprusside relaxation in mice aorta. Sodium nitroprusside induced relaxation in endothelium‐intact (e+) and endothelium‐denuded (e−) aortas with greater potency in e+ than in e−. The nitric oxide synthase inhibitor did not alter the sodium nitroprusside relaxation in both e+ and e− aortas. However, the superoxide anion scavenger abolished the difference in sodium nitroprusside potency between e+ and e−. Sodium nitroprusside reduced dihydroethidium‐derived fluorescent products in both groups; however, the difference between intact and denuded mice aorta remains. The glutathione levels and basal antioxidant activity of superoxide dismutase were reduced in e− aorta when compared with e+, and these values were not altered by sodium nitroprusside. Confirming these results, the levels of lipid peroxidation in e+ were significantly lower when compared to e−, and these values were not altered by sodium nitroprusside. The sodium nitroprusside potency in the presence of a nonselective
COX
inhibitor or the
EP
/
DP
prostaglandin receptor antagonist in endothelium denuded was similar to that in intact mice aorta. Based on these results, we performed the
COX
‐1 and
COX
‐2
mRNA
level studies, and in denuded mice aorta, there was an upregulation in
COX
‐1
mRNA
levels. Taken together, our findings show that in the absence of endothelium, there is an enhancement of superoxide levels, leading to
GSH
consumption and higher levels of lipid peroxidation, showing an intense redox status. Furthermore, in denuded mice aorta, there was an upregulation of
COX
‐1 mRNA expression, leading to vasoconstrictor prostanoids synthesis. The interaction of vasoconstrictor prostanoids with its receptors
EP
/
DP
negatively modulates the vascular relaxation induced by
SNP
in denuded mice aorta. |
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ISSN: | 0767-3981 1472-8206 |
DOI: | 10.1111/fcp.12103 |