Soluble guanylyl cyclase stimulators and activators: Promising drugs for the treatment of hypertension?
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, přehledy
PubMed
39645219
DOI
10.1016/j.ejphar.2024.177175
PII: S0014-2999(24)00865-3
Knihovny.cz E-zdroje
- MeSH
- agonisté guanylátcyklasy terapeutické užití farmakologie MeSH
- aktivátory enzymů terapeutické užití farmakologie MeSH
- antihypertenziva * terapeutické užití farmakologie MeSH
- guanosinmonofosfát cyklický * metabolismus MeSH
- hypertenze * farmakoterapie patofyziologie MeSH
- lidé MeSH
- oxid dusnatý metabolismus MeSH
- rozpustná guanylátcyklasa * metabolismus MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- agonisté guanylátcyklasy MeSH
- aktivátory enzymů MeSH
- antihypertenziva * MeSH
- guanosinmonofosfát cyklický * MeSH
- oxid dusnatý MeSH
- rozpustná guanylátcyklasa * MeSH
Nitric oxide (NO)-stimulated cyclic guanosine monophosphate (cGMP) is a key regulator of cardiovascular health, as NO-cGMP signalling is impaired in diseases like pulmonary hypertension, heart failure and chronic kidney disease. The development of NO-independent sGC stimulators and activators provide a novel therapeutic option to restore altered NO signalling. sGC stimulators have been already approved for the treatment of pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), and chronic heart failure (HFrEF), while sGC activators are currently in phase-2 clinical trials for CKD. The best characterized effect of increased cGMP via the NO-sGC-cGMP pathway is vasodilation. However, to date, none of the sGC agonists are in development for hypertension (HTN). According to WHO, the global prevalence of uncontrolled HTN continues to rise, contributing significantly to cardiovascular mortality. While there are effective antihypertensive treatments, many patients require multiple drugs, and some remain resistant to all therapies. Thus, in addition to improved diagnosis and lifestyle changes, new pharmacological strategies remain in high demand. In this review we explore the potential of sGC stimulators and activators as novel antihypertensive agents, starting with the overview of NO-sGC-cGMP signalling, followed by potential mechanisms by which the increase in cGMP may regulate vascular tone and BP. These effects may encompass not only acute vasodilation, but also mid-term and chronic effects, such as the regulation of salt and water balance, as well as mitigation of vascular ageing and remodelling. The main section summarizes the preclinical and clinical evidence supporting the BP-lowering efficacy of sGC agonists.
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