Soluble Guanylate Cyclase Redox State Under Hypoxia or Hypoxia/Reoxygenation in Isolated Monkey Coronary Arteries

Tawa, Masashi; Geddawy, Ayman; Shimosato, Takashi; Iwasaki, Hiromichi; Imamura, Teruhiko; Okamura, Tomio

doi:10.1254/jphs.14046fp

Cited by 16 publications

(20 citation statements)

References 29 publications

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“…In the previous study, we have shown that superoxide, a precursor of peroxynitrite, has an ability to shift the sGC redox equilibrium toward the NO-insensitive form in isolated endothelium-denuded monkey coronary [22] and rat iliac arteries [21]. Based on this observation, we next examined whether superoxide contributes to the effects of peroxynitrite on the relaxant responses to BAY compounds.…”

Section: Discussionmentioning

confidence: 99%

“…The content of cGMP in endothelium-denuded rat iliac artery strips was measured according to the method described previously with minor modifications [22]. Briefly, the strips were incubated without (referred to as ‘basal') and with BAY 41-2272 (10 -7 M ) or BAY 60-2770 (10 -9 M ) for about 20 min after exposing to each condition and were then immediately plunged into liquid nitrogen.…”

Section: Methodsmentioning

confidence: 99%

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Effects of Peroxynitrite on Relaxation through the NO/sGC/cGMP Pathway in Isolated Rat Iliac Arteries

et al. 2014

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Background/Aims: The present study investigated the mechanism by which peroxynitrite impairs vascular function through the nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP pathway. Methods: Mechanical responses of rat external iliac arteries without endothelium were studied under exposure to peroxynitrite. cGMP concentrations were determined by enzyme immunoassay. Results: Relaxation induced by BAY 41-2272 (sGC stimulator) was impaired under exposure to peroxynitrite, whereas that by BAY 60-2770 (sGC activator) was enhanced. These responses were correlated with tissue levels of cGMP. Effects of peroxynitrite on the relaxant responses to BAY compounds were also observed in the presence of superoxide dismutase (SOD) or tempol, both of which scavenge a certain kind of reactive molecules other than peroxynitrite. As is the case with the relaxant response to BAY 41-2272, acidified NaNO₂- and nitroglycerin-induced relaxations were markedly attenuated by exposing the arteries to peroxynitrite, which was not abolished by preincubation with SOD or tempol. On the other hand, peroxynitrite exposure had no effect on the 8-Br-cGMP-induced vasorelxation. Conclusion: These findings suggest that peroxynitrite interferes with the NO/sGC/cGMP pathway by altering the redox state of sGC. It is likely that peroxynitrite can shift the sGC redox equilibrium to the NO-insensitive state in the vasculature.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effects of Peroxynitrite on Relaxation through the NO/sGC/cGMP Pathway in Isolated Rat Iliac Arteries

et al. 2014

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“…Briefly, increased intracellular superoxide scavenges nitroglycerin-derived NO within the smooth muscle [10] and oxidizes sGC heme to the NO-insensitive state [18], both of which result in a decrease in NO bioavailability in the coronary artery. On the other hand, Zheng et al [9] demonstrated that hypoxia increases sGC dimerization probably through superoxide overproduction in porcine coronary arteries.…”

Section: Discussionmentioning

confidence: 99%

Responsiveness of Coronary Arteries to Nitroglycerin under Hypoxia: The Importance of the Endothelium

Tawa

Shimosato²,

Saito³

et al. 2017

Pharmacology

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Background/Aims: Nitroglycerin is widely used as a coronary vasodilator in the treatment of ischemic heart diseases. This study investigated the influence of hypoxia on nitroglycerin-induced relaxation in endothelium-intact and -denuded rabbit, monkey, and porcine coronary arteries. Methods: Helically cut strips of coronary arteries were suspended in organ chambers, and isometric tension was recorded. Results: Nitroglycerin concentration dependently relaxed endothelium-intact rabbit coronary arteries, which were not different under normoxic and hypoxic conditions. On the other hand, nitroglycerin-induced relaxation of endothelium-denuded arteries was significantly attenuated by hypoxia. Similarly, the relaxant response of endothelium-intact monkey coronary arteries to nitroglycerin was not affected by hypoxia, whereas that of endothelium-denuded arteries was impaired. As is the case with rabbit and monkey coronary arteries, exposure to hypoxia resulted in impaired relaxation by nitroglycerin in endothelium-denuded but not endothelium-intact porcine coronary arteries. Conclusion: These findings suggest that coronary endothelium plays a pivotal role in preventing the hypoxia-induced impairment of nitroglycerin responsiveness, regardless of the animal species.

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“…The efficacy of this type of drug has been suggested to be enhanced under oxidative stress, which is causally involved in many cardiovascular diseases (Stasch et al 2006), so its clinical application is highly desirable. In this regard, basic research has shown the utility of sGC activators in the therapy for coronary artery disease (Bice et al 2014;Tawa et al 2014) and heart failure (Boerrigter et al 2007;Fraccarollo et al 2014). Therefore, it may be possible to use sGC activators as substitute drugs for organic nitrates.…”

Section: Introductionmentioning

confidence: 99%

Vasorelaxing effects of the soluble guanylyl cyclase activator BAY 60-2770 in nitrate-tolerant monkey and canine coronary arteries

Tawa

Shimosato

Iwasaki

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Nitrate tolerance is an important problem in the treatment of ischemic heart diseases. The present study investigated whether or not a soluble guanylyl cyclase (sGC) activator can be used as a coronary vasodilator under nitrate-tolerant conditions. Helically cut strips of endothelium-denuded monkey and canine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by a 1-h treatment with nitroglycerin (0.1 mM) followed by 1-h washout of the agent. Control strips were not exposed previously to nitroglycerin, but otherwise were treated identically. The relaxant response to nitroglycerin was dramatically impaired by previous exposure to the drug for 1 h in either monkey or canine coronary arteries, indicating the development of nitrate tolerance. In contrast, development of nitrate tolerance did not affect the relaxant potency and efficacy of the sGC activator BAY 60-2770 in either the monkey or canine coronary arteries. These findings suggest that it may be possible to use sGC activators as substitute drugs for nitroglycerin if tolerance is developed during the treatment of ischemic heart diseases.

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Soluble Guanylate Cyclase Redox State Under Hypoxia or Hypoxia/Reoxygenation in Isolated Monkey Coronary Arteries

Cited by 16 publications

References 29 publications

Effects of Peroxynitrite on Relaxation through the NO/sGC/cGMP Pathway in Isolated Rat Iliac Arteries

Effects of Peroxynitrite on Relaxation through the NO/sGC/cGMP Pathway in Isolated Rat Iliac Arteries

Responsiveness of Coronary Arteries to Nitroglycerin under Hypoxia: The Importance of the Endothelium

Vasorelaxing effects of the soluble guanylyl cyclase activator BAY 60-2770 in nitrate-tolerant monkey and canine coronary arteries

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