Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications

Nossaman, Bobby D.; Pankey, Edward A.; Kadowitz, Philip J.

doi:10.1155/2012/290805

Cited by 49 publications

(59 citation statements)

References 138 publications

(174 reference statements)

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“…These results was confirmed by two different methods of NO quantification, including fluorescence (by using DAF-2DA) measuring the intracellular NO and by electrode measuring through conversion of nitrite (stable metabolite) to NO. Ataciguat is able to induce cGMP accumulation [21] which can activates NOS in endothelial cells, considering that the endothelium treatment with cGMP analogue also stimulated the NO production by NOS activation. Our results suggested that NO production is by a mechanism dependent of NOS activation, and independent of Ca 2+ influx.…”

Section: Discussionmentioning

confidence: 99%

In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

Martinelli¹,

Rodrigues²,

Moraes³

et al. 2018

J Pharm Pharm Sci

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-Purpose. In endothelial cells, investigate if the soluble guanylate cyclase (sGC) activation or stimulation is able to potentiate the relaxation in vessels. Methods. Aortic and coronary rings with and without endothelium were placed in a myograph and cumulative concentration-effect curves for DETA-NO or ataciguat were performed. Nitric oxide (NO) were measured by fluorescence or by selective electrode in human umbilical endothelial cells (HUVECs) in response to some treatments, including ataciguat, 8-BrcGMP and A23187. Results. The presence of the endothelium potentiated the relaxation induced by DETA-NO in aortic and coronary rings. In addition, in aortic rings the endothelium potentiated the relaxation induced by ataciguat. In the presence of nitric oxide synthase (NOS) inhibitor, the endothelium effect was abolished to DETA-NO or ataciguat, in both vessels. Ataciguat, 8-Br-cGMP and A23187 were able to induce NO production in HUVECs cells. In the presence of NOS inhibitor, the NO production induced by ataciguat and 8-Br-cGMP was abolished. Conclusions. Our results suggest that in aortic and coronary rings the endothelium potentiates the relaxation induced by activation or stimulation of sGC through a mechanism dependent of NOS activation.

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Section: Discussionmentioning

confidence: 99%

In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

Martinelli¹,

Rodrigues²,

Moraes³

et al. 2018

J Pharm Pharm Sci

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“…По оси абсцисс -варианты комбинированного воздействия препаратов; аддитивный вклад веществ в комбина-ции отражают столбцы (YC-1+SNP)* и (ТФ+YC-1+SNP)**. Данные представлены в виде М ± m из трех независимых экспериментов В заключение этого раздела следует отметить, что ТФ, пополняя ряды регуляторов рГЦ [74] (рис. 5), представ-ляет интерес для исследователей.…”

Section: исследования влияния тф на функциональную активность ргц троunclassified

Soluble Guanylyl Cyclase (sGC) in Mechanisms of Hypotensive and Antiaggregatory Effects Induced by Teraphtal (TP, sodium salt 4,5-cardoxyphtalQcyanin-cobalt)

Ta¹,

Nv²,

Is³

et al. 2016

Клиническая онкогематология

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Background & Aims. Many antitumor drugs produces not only the variety of therapeutic effects but also a broad spectrum of side effects, including acute hemodynamic dysfunctions (hypotension/hypertension, coagulation disorders). The aim of the paper is to investigate the role of soluble guanylyl cyclase (sGC) in mechanisms of hypotensive and antiaggregatory effects induced by teraphtal (TP) under experimental conditions in the clinic. Methods. The effect of different products on the basal activity of sGC isolated from platelets of human peripheral blood was assessed by the immunoenzyme method based on production of cyclic guanosine monophosphate (cGMP). The effect of TP on ADP-induced human platelet aggregation was evaluated by the turbidimetric Born method using an aggregometer. Results. In the presence of TP, the basal sGC activity increased by the average of 2.5-fold. The TP-induced dose-response curve of sGC activation displays a bell-shaped behavior with maximal stimulation effect achieved at a concentration of 1 μmol/L. TP does not affect the sGC activation induced by known sGC regulators, such as sodium nitroprusside (SNP) and YC-1. On the other hand, after preliminary incubation of sGC with TP, the ability of YC-1 to potentiate the enzyme stimulation induced by SNP decreased by about 33 %. In vitro tests demonstrated the ability of TP to inhibit the ADP-induced platelet aggregation and established the IC<sub>50</sub> value for TP (15 μmol/L). Conclusion. TP is a direct sGC activator and therefore is able to participate in regulation of the NO→sGC→cGMP signaling pathway that controls the basal vascular tone and aggregatory platelet properties. Taking into account the TP characteristics, the paper discusses the involvement of additional mechanisms in the development of hypotension and hemostatic disorders induced by the drug.

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“…In conditions associated with incremented oxidative stress, NO generation, diminished biological availability can lead to NO donor tolerance with prolonged use [24]. Two classes of compounds that activate sGC by NO-independent pathways are under investigation: sGC stimulators and sGC activators.…”

Section: Stimulators and Activators Of Soluble Guanylate Cyclasementioning

confidence: 99%

“…Riociguat significantly reduced systolic BP and systemic vascular resistance [25]. Activators of sGC can increase sGC enzyme activity even when it is oxidized and less responsive to NO [24]. BAY 58-2667 (Cinaciguat)…”

Section: Stimulators and Activators Of Soluble Guanylate Cyclasementioning

confidence: 99%

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Novel Molecules

Vukelic¹,

Orías²

2014

Chronic Kidney Disease and Hypertension

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Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications

Cited by 49 publications

References 138 publications

In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

Soluble Guanylyl Cyclase (sGC) in Mechanisms of Hypotensive and Antiaggregatory Effects Induced by Teraphtal (TP, sodium salt 4,5-cardoxyphtalQcyanin-cobalt)

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