A novel cardioprotective mechanism of exogenous nitric oxide: inhibition of Rho-associated kinase activity

Tanaka, Atsushi; Node, Koichi

doi:10.1038/hr.2015.61

Cited by 2 publications

(1 citation statement)

References 13 publications

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“…To evaluate the molecular mechanisms underlying the inhibitory effect of adiponectin on ROS formation and p22 phox mRNA expression in Ang II-stimulated aortic rings, we investigated the influence of the NO synthesis inhibitor L -NAME on adiponectin’s anti-oxidant effect. NO has many cardioprotective actions on the cardiovascular system during hypertension ( Tanaka and Node, 2015 ). The major functions of NO on the cardiovascular system include anti-inflammatory, anti-proliferative, anti-thrombotic, and anti-hypertrophic activity ( Tziros and Freedman, 2006 ; Garcia and Incerpi, 2008 ; Momi et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Remodeling through Nitric Oxide and the RhoA/ROCK Pathway

et al. 2016

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Introduction: Adiponectin (APN), an adipocytokine, exerts protective effects on cardiac remodeling, while angiotensin II (Ang II) induces hypertension and vascular remodeling. The potential protective role of APN on the vasculature during hypertension has not been fully elucidated yet. Here, we evaluate the molecular mechanisms of the protective role of APN in the physiological response of the vascular wall to Ang II.Methods and Results: Rat aortic tissues were used to investigate the effect of APN on Ang II-induced vascular remodeling and hypertrophy. We investigated whether nitric oxide (NO), the RhoA/ROCK pathway, actin cytoskeleton remodeling, and reactive oxygen species (ROS) mediate the anti-hypertrophic effect of APN. Ang II-induced protein synthesis was attenuated by pre-treatment with APN, NO donor S-nitroso-N-acetylpenicillamine (SNAP), or cGMP. The hypertrophic response to Ang II was associated with a significant increase in RhoA activation and vascular force production, which were prevented by APN and SNAP. NO was also associated with inhibition of Ang II-induced phosphorylation of cofilin. In addition, immunohistochemistry revealed that 24 h Ang II treatment increased the F- to G-actin ratio, an effect that was inhibited by SNAP. Ang II-induced ROS formation and upregulation of p22phox mRNA expression were inhibited by APN and NO. Both compounds failed to inhibit Nox1 and p47phox expression.Conclusion: Our results suggest that the anti-hypertrophic effects of APN are due, in part, to NO-dependent inhibition of the RhoA/ROCK pathway and ROS formation.

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Section: Discussionmentioning

confidence: 99%

Adiponectin Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Remodeling through Nitric Oxide and the RhoA/ROCK Pathway

et al. 2016

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Effect of chemical structure of S-nitrosothiols on nitric oxide release mediated by the copper sites of a metal organic framework based environment

Taylor-Edinbyrd

Kumar

2017

Phys. Chem. Chem. Phys.

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The effect of chemical structure of different biologically compatible S-nitrosothiols on the solvation environment at catalytic copper sites in a metal organic framework (MOF) suspended in a solution of ethanol is probed using computational methods. The use of a copper based MOF as a storage vehicle and catalyst (copper sites of the MOF) in the controlled and sustained release of chemically stored nitric oxide (NO) from S-nitrosocysteine has been shown to occur both experimentally and computationally [J. Am. Chem. Soc., 2012, 134, 3330-3333; Phys. Chem. Chem. Phys., 2015, 17, 23403]. Previous studies on a copper based MOF, namely HKUST-1, concluded that modifications in the R-group of s-nitrosothiols and/or organic linkers of MOFs led to a method capable of modulating NO release. In order to test the hypothesis that larger R-groups slow down NO release, four different RSNOs (R = cysteine, N-acetylcysteine, N-acetyl-d,l-penicillamine or glutathione) of varying size were investigated, which in turn required the use of a larger copper based MOF. Due to its desirable copper centers and more extensive framework, MOF-143, an analog of HKUST-1 was chosen to further explore both the effect of different RSNOs as well as MOF environments on NO release. Condensed phase classical molecular dynamics simulations are utilized to study the effect of the complex MOF environment as well as the chemical structure and size of the RSNO on the species on the catalytic reaction. The results indicate that in addition to the size of the RSNO species and the organic linkers within the MOF, the reaction rates can be modulated by the molecular structure of the RSNO and furthermore combining different RSNO species can also be used to tune the rate of NO release.

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A novel cardioprotective mechanism of exogenous nitric oxide: inhibition of Rho-associated kinase activity

Cited by 2 publications

References 13 publications

Adiponectin Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Remodeling through Nitric Oxide and the RhoA/ROCK Pathway

Adiponectin Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Remodeling through Nitric Oxide and the RhoA/ROCK Pathway

Effect of chemical structure of S-nitrosothiols on nitric oxide release mediated by the copper sites of a metal organic framework based environment

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