In vitro Treatment with cis-[Ru(H-dcbpy-)2(Cl)(NO)] Improves the Endothelial Function in Aortic Rings with Endothelial Dysfunction

Oishi, Jorge; Buzinnari, Tereza Cristina; Pestana, Cezar Rangel; Moraes, Thiago Francisco de; Vatanabe, Izabela Pereira; Wink, David A.; Silva, Roberto Santana da; Bendhack, Lusiane Maria; Rodrigues, Gerson Jhonatan

doi:10.18433/j3cc9k

Cited by 13 publications

(11 citation statements)

References 33 publications

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“…As a result, EC viability, migration and angiogenesis for cells treated with SA-2 were increased while ones treated with reference drugs were not. Similar to our findings, a low dose of an NO donor DCBPY (cis-[Ru(H-dcbpy − ) 2 (Cl)(NO)]) to HUVECs provided NO at the same level as the control groups, and therefore induced relaxation of aortic rings and improved EC functions 37 . This result is in support of our results where SA-2 at 0.5 µM provided a physiological NO production, improved EC viability, and facilitated angiogenesis under stress conditions.…”

Section: Discussionsupporting

confidence: 89%

Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases

Kuriakose

Nguyen

et al. 2017

Sci Rep

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Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress. Compound SA-2 scavenged reactive oxygen species, inhibited proliferation and migration of smooth muscle cells (SMCs) and promoted the tube formation from ECs. Copolymer poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with SA-2 provided a sustained release of NO over days, improved aqueous stability in serum, protected ECs against oxidative stress, and enhanced angiogenesis under stress conditions as compared to that of the control in the in vitro matrigel tube formation assay. These results indicated the potential use of SA-2 nanoparticles as an alternative therapy to treat PAD.

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Section: Discussionsupporting

confidence: 89%

Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases

Kuriakose

Nguyen

et al. 2017

Sci Rep

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“…These results are in accordance with previous study, that have shown an improvement on endothelial function by aortic rings treatment with 0.1 µ M of another ruthenium compound ( cis- [Ru(H-dcbpy - ) 2 (Cl)(NO)]). 4 Thus, some results have suggested that ruthenium compounds can release NO and improve the endothelial function, which is a desirable effect on vascular system when endothelial dysfunction is present.…”

Section: Discussionmentioning

confidence: 99%

“…On preliminary results, we have observed that the ruthenium complex cis- [Ru(H-dcbpy) 2 (Cl)(NO)] (dcbpy) improved the relaxation endothelium dependent induced by acetylcholine in aortic rings from hypertensive rats 4 . This compound also is able to induce relaxation by NO release in higher concentration, and the improvement in endothelial function was attributed to inactivation of O 2 - .…”

Section: Introdutionmentioning

confidence: 97%

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Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats

Vatanabe¹,

Rodrigues²,

Buzinari³

et al. 2017

Arquivos Brasileiros De Cardiologia

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BackgroundThe endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases.ObjectiveVerify if cis- [Ru(bpy)2(NO2)(NO)](PF6)2 (BPY) improves endothelial function and the sensibility of conductance (aorta) and resistance (coronary) to vascular relaxation induced by BPY.MethodsNormotensive (2K) and hypertensive (2K-1C) Wistar rats were used. For vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: BPY(0.01 to10 µM) and concentration effect curves to acetylcholine were performed. In addition, cumulative concentration curves were performed to BPY (1.0 nM to 0.1 µM) in aortic and coronary rings, with intact and denuded endothelium.ResultsIn aorta from 2K-1C animals, the treatment with BPY 0.1µM increased the potency of acetylcholine-induced relaxation and it was able to revert the endothelial dysfunction. The presence of the endothelium did not modify the effect of BPY in inducing the relaxation in aortas from 2K and 2K-1C rats. In coronary, the endothelium potentiated the vasodilator effect of BPY in vessels from 2K and 2K-1C rats.ConclusionOur results suggest that 0.1 µM of BPY is able to normalize the relaxation endothelium dependent in hypertensive rats, and the compound BPY induces relaxation in aortic from normotensive and hypertensive rats with the same potency. The endothelium potentiate the relaxation effect induced by BPY in coronary from normotensive and hypertensive rats, with lower effect on coronary from hypertensive rats.

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“…13 The aortas were carefully dissected and mounted as ring preparations (≅4 mm in length) and placed in bath chambers (5 mL) containing Krebs solution at 37 °C (NaCl 130mM, KCl 47 mM, KH 2 PO 4 1.2 mM, CaCl 1.6; MgSO 4 1.2mM; NaHCO 3 14.9 mM; glucose 5.5 mM) continuously bubbled with 95% O 2 and 5% CO 2 , pH 7.4, in a Mulvany-Halpern isometric myograph (model 610 DMT-USA, Marietta, GA) and recorded by a PowerLab8/SP data acquisition system (AD Instruments Pty Ltd., Colorado Springs, CO). The aortic rings were submitted to a tension of 1.5 g, which was readjusted every 15 min for a 60-min equilibration period before addition of the given drug.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats

Fabrício

Oishi

Biffe

et al. 2017

Arquivos Brasileiros De Cardiologia

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BackgroundDespite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure).ObjectiveTo verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. Methods3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. ResultsOvariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. ConclusionOur results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats.

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In vitro Treatment with cis-[Ru(H-dcbpy-)2(Cl)(NO)] Improves the Endothelial Function in Aortic Rings with Endothelial Dysfunction

Cited by 13 publications

References 33 publications

Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases

Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases

Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats

Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats

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