Participation of Nitric Oxide Pathway in the Relaxation Response Induced by E-cinnamaldehyde Oxime in Superior Mesenteric Artery Isolated From Rats

Veras, Robson Cavalcante; Rodrigues, Karoline G.; Alustau, Maria Do Carmo de; Araújo, Islania Giselia Albuquerque; Barros, André Luís Branco de; Alves, Ricardo José; Nakao, Lia S.; Braga, Valdir de Andrade; Silva, Darízy F.; Medeiros, Isac A.

doi:10.1097/fjc.0b013e31829013ff

Cited by 19 publications

(30 citation statements)

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“…These data suggest the involvement of the NO-sGC-cGMP pathway in the relaxant response induced by Oxime S1. In a similar way, Chalupský et al and Veras et al [13,14] demonstrated that the effects of several non-aromatic substituted oximes derivatives involve the NO-sGC-cGMP pathway.…”

Section: Oxime S1 Produces Vasorelaxation Via Activation Of the No-sgmentioning

confidence: 80%

“…It has been reported that non-amino acid compounds sharing the R 2 C=NOH group can produce nitric oxide synthase-independent relaxation in endothelium-denuded aortic rings of rats [10,[14][15][16]. In addition, the mechanisms underlying the effects of exogenous nitrovasodilators are predominantly mediated by cyclic guanosine monophosphate (cGMP), as a result of the activation of soluble guanylyl cyclase [17,18].…”

Section: Figurementioning

confidence: 99%

“…In fact, we have documented that oximes bearing a R 2 C=NOH group are able to release nitric oxide by using the NO indicator diaminofluorescein 4,5-diacetate [14]. The vasorelaxant responses induced by Oxime S1 (10 −8 to 10 −4 M) in aorta rings were reduced by hydroxocobalamin (30 µM), an NO extracellular scavenger, when compared to control (E max = 68% ± 4% vs. 94% ± 4%; and pD 2 = 4.83 ± 0.04 vs. 5.20 ± 0.04, p < 0.05, respectively), and by methylene blue (10 µM), an inhibitor of sGC (E max = 67% ± 5% versus 94% ± 4%; and pD 2 = 4.85 ± 0,04 versus 5.2 ± 0.04, p < 0.05) ( Figure 5).…”

Section: Oxime S1 Produces Vasorelaxation Via Activation Of the No-sgmentioning

confidence: 99%

“…Previous studies aiming to evaluate the vascular effects induced by oximes were performed in arteries without endothelium suggesting the involvement of the NO-cGMP pathway [13,14]. The aim of the present study was to investigate the cardiovascular effects produced by a new synthetized oxime, the 3-hydroxy-4-(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1, Figure 1), which is a semi-natural naphthoquinone derivative of lapachol extracted from Tabebuia avallanedae Lor.Ex.Gris (Bignoniaceae), which formula is shown bellow.…”

Section: Introductionmentioning

confidence: 99%

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Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

et al. 2014

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It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4-(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10,15, 20 and 30 mg/Kg, i.v.) produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10 −8 M to 10 −4 M). In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO) pathway. Additionally, Oxime S1 (30 and 100 µM) significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively) measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM) prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting OPEN ACCESSMolecules 2014, 19 9774 a role for potassium channels, more precisely K ir , K v and K ATP channels. We observed the involvement of BK Ca channels in Oxime S1-induced relaxation in mesenteric artery rings.In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC) and K + channels.

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Section: Oxime S1 Produces Vasorelaxation Via Activation Of the No-sgmentioning

confidence: 80%

Section: Figurementioning

confidence: 99%

Section: Oxime S1 Produces Vasorelaxation Via Activation Of the No-sgmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

et al. 2014

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“…Previous publications reported that aryl oximes could be metabolized by cytochrome P450 and NO synthase to release NO [1, 10, 52]. Because of the biological effects of NO during reperfusion, we studied whether the aryl oxime IQ-1S could act as a NO precursor after an in situ oxidation catalyzed by endogenous enzymes under physiological conditions (liver microsomes with NADPH and O 2 ).…”

Section: Resultsmentioning

confidence: 99%

A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia–reperfusion injury in mice

Atochin

Schepetkin

Khlebnikov

et al. 2016

Neuroscience Letters

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The c-Jun N-terminal kinase (JNK) has been shown to be an important regulator of neuronal cell death. Previously, we synthesized the sodium salt of 11H-indeno[1,2-b]quinoxalin-11-one (IQ-1S) and demonstrated that it was a high-affinity inhibitor of the JNK family. In the present work, we found that IQ-1S could release nitric oxide (NO) during its enzymatic metabolism by liver microsomes. Moreover, serum nitrite/nitrate concentration in mice increased after intraperitoneal injection of IQ-1S. Because of these dual actions as JNK inhibitor and NO-donor, the therapeutic potential of IQ-1S was evaluated in an animal stroke model. We subjected wild-type C57BL6 mice to focal ischemia (30 minutes) with subsequent reperfusion (48 hours). Mice were treated with IQ-1S (25 mg/kg) suspended in 10% solutol or with vehicle alone 30 minutes before and 24 hours after middle cerebral artery MCA) occlusion (MCAO). Using laser-Doppler flowmetry, we monitored cerebral blood flow (CBF) above the MCA during 30 minutes of MCAO provoked by a filament and during the first 30 minutes of subsequent reperfusion. In mice treated with IQ-1S, ischemic and reperfusion values of CBF were not different from vehicle-treated mice. However, IQ-1S treated mice demonstrated markedly reduced neurological deficit and infarct volumes as compared with vehicle-treated mice after 48 hours of reperfusion. Our results indicate that the novel JNK inhibitor releases NO during its oxidoreductive bioconversion and improves stroke outcome in a mouse model of cerebral reperfusion. We conclude that IQ-1S is a promising dual functional agent for the treatment of cerebral ischemia and reperfusion injury.

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The effects of Cinnamaldehyde on early brain injury and cerebral vasospasm following experimental subarachnoid hemorrhage in rabbits

et al. 2019

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The neuroprotective and vasodilatory effects of cinnamaldehyde have been widely studied and documented. On the basis of these findings, we hypothesized that cinnamaldehyde exhibits therapeutic effects on subarachnoid hemorrhage-induced early brain injury and cerebral vasospasm. Thirty-two adult male New Zealand white rabbits were randomly divided into four groups of eight rabbits: control, subarachnoid hemorrhage, subarachnoid hemorrhage + vehicle, and subarachnoid hemorrhage + cinnamaldehyde. An intraperitoneal dose of 50 mg/kg cinnamaldehyde was administered 5 min following an intracisternal blood injection, followed by three further daily injections at identical doses. The animals were sacrificed 72 h after subarachnoid hemorrhage was induced. The crosssectional areas and arterial wall thicknesses of the basilar artery were measured and hippocampal degeneration scores were evaluated. Treatment with cinnamaldehyde was effective in providing neuroprotection and attenuating cerebral vasospasm after subarachnoid hemorrhage in rabbits. It effectively increased the cross-sectional areas of the basilar artery and reduced the arterial wall thickness; in addition, hippocampal degeneration scores were lower in the cinnamaldehyde group. The findings of this study showed, for the first time to our knowledge, that cinnamaldehyde exhibits neuroprotective activity against subarachnoid hemorrhage-induced early brain injury and that it can prevent vasospasm. Potential mechanisms underlying the neuroprotection and vasodilation were discussed. Cinnamaldehyde could play a role in subarachnoid hemorrhage treatment.

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Participation of Nitric Oxide Pathway in the Relaxation Response Induced by E-cinnamaldehyde Oxime in Superior Mesenteric Artery Isolated From Rats

Cited by 19 publications

References 60 publications

Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia–reperfusion injury in mice

The effects of Cinnamaldehyde on early brain injury and cerebral vasospasm following experimental subarachnoid hemorrhage in rabbits

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