Pharmacological developments in antihypertensive treatment through nitric oxide—cGMP modulation

Jüttner, Annika A.; Danser, A.H. Jan; Roks, Anton J.M.

doi:10.1016/bs.apha.2022.01.001

Cited by 4 publications

(3 citation statements)

References 152 publications

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“…Prolonged, strong increase of cGMP has been linked to dimerization of the effector protein kinase G (PKG). In turn, PKG dimerization has been shown to activate of BK Ca2+ channels in VSMC, a process that can also take place independently from cGMP through redox regulation and PKG oxidation (Ataei Ataabadi et al, 2020 ; Burgoyne et al, 2012 ; Feelisch et al, 2020 ; Jüttner & Roks, 2022 ; Sheehe et al, 2018 ). EDH involves an intricate interplay between endothelial and VSMC K + channels (Goto & Kitazono, 2019 ), which can bring these two signaling changes together.…”

Section: Discussionmentioning

confidence: 99%

Soluble guanylate cyclase activator BAY 54–6544 improves vasomotor function and survival in an accelerated ageing mouse model

et al. 2022

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DNA damage is a causative factor in ageing of the vasculature and other organs. One of the most important vascular ageing features is reduced nitric oxide (NO)soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling. We hypothesized that the restoration of NO-sGC-cGMP signaling with an sGC activator (BAY 54-6544) may have beneficial effects on vascular ageing and premature death in DNA repair-defective mice undergoing accelerated ageing. Eight weeks of treatment with a non-pressor dosage of BAY 54-6544 restored the decreased in vivo microvascular cutaneous perfusion in progeroid Ercc1 ∆/− mice to the level of wild-type mice. In addition, BAY 54-6544 increased survival of Ercc1 ∆/− mice. In isolated Ercc1 ∆/− aorta, the decreased endothelium-independent vasodilation was restored after chronic BAY 54-6544 treatment. Senescence markers p16 and p21, and markers of inflammation, including Ccl2, Il6 in aorta and liver, and circulating IL-6 and TNFα were increased in Ercc1 ∆/− , which was lowered by the treatment. Expression of antioxidant genes, including Cyb5r3 and Nqo1, was favorably changed by chronic BAY 54-6544 treatment.In summary, BAY 54-6544 treatment improved the vascular function and survival rates in mice with accelerated ageing, which may have implication in prolonging health span in progeria and normal ageing.

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Section: Discussionmentioning

confidence: 99%

Soluble guanylate cyclase activator BAY 54–6544 improves vasomotor function and survival in an accelerated ageing mouse model

et al. 2022

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“…NO therefore plays a dual role: it has a protective effect in non-specific immune defense, and it also has toxic and pro-inflammatory effects and mediates various symptoms of inflammation, oxidative stress and septic shock [ 51 ]. There are several therapeutic applications of the modulation of NOS pathways and the direct administration of low-dose NO including the treatment of hypertension, peripheral arterial disease, sepsis and acute respiratory failure [ 51 , 52 , 53 , 54 , 55 ].…”

Section: Exhaled Gaso-transmittersmentioning

confidence: 99%

Exhaled Biomarkers for Point-of-Care Diagnosis: Recent Advances and New Challenges in Breathomics

et al. 2023

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Cancers, chronic diseases and respiratory infections are major causes of mortality and present diagnostic and therapeutic challenges for health care. There is an unmet medical need for non-invasive, easy-to-use biomarkers for the early diagnosis, phenotyping, predicting and monitoring of the therapeutic responses of these disorders. Exhaled breath sampling is an attractive choice that has gained attention in recent years. Exhaled nitric oxide measurement used as a predictive biomarker of the response to anti-eosinophil therapy in severe asthma has paved the way for other exhaled breath biomarkers. Advances in laser and nanosensor technologies and spectrometry together with widespread use of algorithms and artificial intelligence have facilitated research on volatile organic compounds and artificial olfaction systems to develop new exhaled biomarkers. We aim to provide an overview of the recent advances in and challenges of exhaled biomarker measurements with an emphasis on the applicability of their measurement as a non-invasive, point-of-care diagnostic and monitoring tool.

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“…NO is a crucial regulator of endothelial homeostasis and has multiple biological functions, including stimulating VEGF secretion from endothelial cells and macrophages [ 59 ]. Chin et al, in in vivo murine models, showed that the inhibition of endothelial nitric oxide synthase (eNOS) was associated with the impairment of angiogenesis not because of aging per se but because of all the mechanisms (including endothelial dysfunction, smooth muscle cell disruption, increased oxidative stress, and DNA damage) that mark it [ 60 , 61 ]. Although eNOS represents the primary source of NO in the vascular endothelium, neuronal NOS (nNOS) also contributes to endothelial cells-derived NO.…”

Section: Endothelial Dysfunction and Impaired Angiogenesis In The Eld...mentioning

confidence: 99%

Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases

Pacinella

Ciaccio

Tuttolomondo

2022

IJMS

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Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized over the years. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are the main characteristics of the aged organism; they represent the framework within which an enormous array of molecular abnormalities occur and contribute to accelerating and perpetuating the decline of organs and tissues. Recognizing and detailing each of these dysfunctional pathways is helpful for therapeutic purposes, as it allows one to hypothesize the possibility of tailoring interventions to the damaged mechanism and hypothetically limiting the cascade of events that drive the onset of these diseases. With this paper, we have reviewed the scientific literature, analysing the pathophysiological basis of the vascular diseases of the elderly and pausing to reflect on attempts to interrupt the vicious cycle that connotes the diseases of aging, laying the groundwork for therapeutic reasoning and expanding the field of scientific research by moving from a solid foundation.

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Pharmacological developments in antihypertensive treatment through nitric oxide—cGMP modulation

Cited by 4 publications

References 152 publications

Soluble guanylate cyclase activator BAY 54–6544 improves vasomotor function and survival in an accelerated ageing mouse model

Soluble guanylate cyclase activator BAY 54–6544 improves vasomotor function and survival in an accelerated ageing mouse model

Exhaled Biomarkers for Point-of-Care Diagnosis: Recent Advances and New Challenges in Breathomics

Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases

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