Nitric oxide-independent stimulation of soluble guanylate cyclase reduces organ damage in experimental low-renin and high-renin models

Sharkovska, Yuliya; Kalk, Philipp; Lawrenz, Bettina; Godes, Michael; Hoffmann, Laura; Wellkisch, Kathrin; Geschka, Sandra; Relle, Katharina; Hocher, Berthold; Stasch, Johannes‐Peter

doi:10.1097/hjh.0b013e32833b558c

Cited by 89 publications

(82 citation statements)

References 28 publications

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“…Ngal has been proposed as a biotarget for cardiovascular fibrosis (40). These results are consistent with other studies using NOsGC stimulators, showing a reduction in cardiac fibrosis in a blood pressure-independent manner (41,42).…”

Section: Discussionsupporting

confidence: 88%

Nitric oxide–sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction

et al. 2018

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Section: Discussionsupporting

confidence: 88%

Nitric oxide–sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction

et al. 2018

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“…Riociguat has effects on vascular and endothelial function that may be beneficial in CTEPH [47][48][49][50][51][52]. Consequently, hybrid therapy (medical treatment combined with BPA and PEA) may be a promising option [9].…”

Section: Current Bpa Practicementioning

confidence: 99%

Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension

et al. 2017

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Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to result from incomplete resolution of pulmonary thromboemboli that undergo organisation into fibrous tissue within pulmonary arterial branches, filling pulmonary arterial lumina with collagenous obstructions. The treatment of choice is pulmonary endarterectomy (PEA) in CTEPH centres, which has low post-operative mortality and good long-term survival. For patients ineligible for PEA or who have recurrent or persistent pulmonary hypertension after surgery, medical treatment with riociguat is beneficial. In addition, percutaneous balloon pulmonary angioplasty (BPA) is an emerging option, and promises haemodynamic and functional benefits for inoperable patients. In contrast to conventional angioplasty, BPA with undersized balloons over guide wires exclusively breaks intraluminal webs and bands, without dissecting medial vessel layers, and repeat sessions are generally required. Observational studies report that BPA improves haemodynamics, symptoms and functional capacity in patients with CTEPH, but controlled trials with long-term follow-up are needed. Complications include haemoptysis, wire injury, vessel dissection, vessel rupture, reperfusion pulmonary oedema, pulmonary parenchymal bleeding and haemorrhagic pleural effusions. This review summarises the available evidence for BPA, patient selection, recent technical refinements and periprocedural imaging, and discusses the potential future role of BPA in the management of CTEPH.

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“…In two independent rat models of hypertension, riociguat had a potent protective effect against cardiac and renal damage. In the first model (low-NO/high-renin), riociguat induced a marked dose-dependent decrease in renal interstitial fibrosis and normalized blood pressure versus control rats [38 ]. In a subtotal nephrectomy rat model, riociguat-treated rats exhibited significantly lower blood pressure compared with untreated sham-operated animals, and had a significantly higher creatinine clearance compared with untreated rats [38 ].…”

Section: Riociguatmentioning

confidence: 96%

“…In the first model (low-NO/high-renin), riociguat induced a marked dose-dependent decrease in renal interstitial fibrosis and normalized blood pressure versus control rats [38 ]. In a subtotal nephrectomy rat model, riociguat-treated rats exhibited significantly lower blood pressure compared with untreated sham-operated animals, and had a significantly higher creatinine clearance compared with untreated rats [38 ]. Furthermore, in a model of chronic volume and pressure overload using salt-sensitive Dahl rats fed a high-salt diet, riociguat significantly reduced glomerulosclerosis and interstitial and perivascular fibrosis, and significantly decreased mortality, compared with vehicle-treated rats [9].…”

Section: Riociguatmentioning

confidence: 98%

Renal effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence

Stasch

Schlossmann

Hocher

2015

Current Opinion in Pharmacology

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Direct stimulation of soluble guanylate cyclase (sGC) is emerging as a potential new approach for the treatment of renal disorders. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), deficiency of which is implicated in the pathogenesis of chronic kidney disease (CKD). Therefore, new classes of drugs - sGC stimulators and activators - are being investigated in preclinical models under conditions where nitric oxide is deficient. In preclinical models with different etiologies of CKD, the sGC stimulators BAY 41-2272, BAY 41-8543, BAY 60-4552, riociguat and vericiguat and the sGC activators cinaciguat, ataciguat, BI 703704 and GSK2181236A have shown consistently renoprotective effects. Clinical trials are required to confirm these findings in humans, and to ascertain whether these agents could provide a future alternative to guideline-recommended treatments.

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Nitric oxide-independent stimulation of soluble guanylate cyclase reduces organ damage in experimental low-renin and high-renin models

Abstract: We demonstrate for the first time that the novel sGC stimulator riociguat shows in two independent models of hypertension a potent protection against cardiac and renal target organ damage.

Cited by 89 publications

References 28 publications

Nitric oxide–sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction

Nitric oxide–sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction

Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension

Renal effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence

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