Inhibition of hyperpolarization‐activated cyclic nucleotide‐gated channels by β‐blocker carvedilol

“…A universally known example of such stereoselectivity is thalidomide, whose R ‐enantiomer has sedative and hypnotic effects, whereas the S ‐enantiomer has teratogenic effects. It has been suggested that the importance of CAR in the treatment of congestive heart failure might contribute to its non‐selectivity and some other properties, which are different from other known β‐blockers, such as Met (Cao et al, ; DiNicolantonio & Hackam, ; Poole‐Wilson et al, ). In this study, the main ingredient of CAR contributing to its antioxidant activity, namely S ‐CAR or R ‐CAR, has been investigated.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of S‐carvedilol on doxorubicin‐induced damages to human umbilical vein endothelial cells and rats

Lan

et al. 2019

J of Applied Toxicology

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Doxorubicin (DOX) is a highly active anticancer drug with severe cytotoxicity, which is strongly associated with oxidative stress. Carvedilol (CAR), used as its racemate with S-CAR and R-CAR (1:1), has been previously reported to ameliorate the DOX-induced cytotoxicity. However, the main contributor from CAR of its protective effects has not been clear. Therefore, in this study, we aimed to investigate further the different effects of CAR enantiomers on DOX-induced cytotoxicity in human umbilical vein endothelial cells and rats, respectively. Results indicated that S-CAR could significantly attenuate DOX-induced cell death, apoptotic morphological changes, decrease the mitochondrial membrane potential and oxidative stress responses by increasing the superoxide dismutase and catalase activities, and decreasing malondialdehyde contents and reactive oxygen species levels via the phosphoinositide 3-kinase/AKT/endothelial nitric oxide synthase pathway in vitro.Consistent with the in vitro study, the protective effects of S-CAR on the myocardial tissues and hemodynamics were also detected in rats suffering because of DOX treatment. With the obtained results, we can first conclude that S-CAR provides superior protection to injury induced by DOX relative to that of racemic CAR and R-CAR.

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“…The development of pharmacotherapeutic agents with proven benefit in the treatment of patients with HFrEF has been progressing rapidly. Guidelines recommend stepwise initiation and up titration of ACE-I, ARBs and beta-blockers, and other pharmacotherapeutics such as mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors and hyperpolarization activated cyclic nucleotide-gated channel blockers may be added [ 10 , 11 ]. Novel agents such as dapagliflozin and omecamtiv mecarbil have shown benefit in reducing mortality in patients with HFpEF [ 12 , 13 ], but improvements in patient outcomes and mortality have not been replicated.…”

Section: Introductionmentioning

confidence: 99%

Novel Oxidative Stress Biomarkers with Risk Prognosis Values in Heart Failure

Yap

et al. 2023

Biomedicines

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Oxidative stress (OS) is mediated by reactive oxygen species (ROS), which in cardiovascular and other disease states, damage DNA, lipids, proteins, other cellular and extra-cellular components. OS is both initiated by, and triggers inflammation, cardiomyocyte apoptosis, matrix remodeling, myocardial fibrosis, and neurohumoral activation. These have been linked to the development of heart failure (HF). Circulating biomarkers generated by OS offer potential utility in patient management and therapeutic targeting. Novel OS-related biomarkers such as NADPH oxidases (sNox2-dp, Nrf2), advanced glycation end-products (AGE), and myeloperoxidase (MPO), are signaling molecules reflecting pathobiological changes in HF. This review aims to evaluate current OS-related biomarkers and their associations with clinical outcomes and to highlight those with greatest promise in diagnosis, risk stratification and therapeutic targeting in HF.

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Inhibition of hyperpolarization‐activated cyclic nucleotide‐gated channels by β‐blocker carvedilol

Abstract: Carvedilol is a negative gating modulator of HCN channels. It represents a novel structure for future drug design of HCN channel inhibitors.

Cited by 12 publications

References 60 publications

Characterizations of the Urate Transporter, GLUT9, and Its Potent Inhibitors by Patch-Clamp Technique

Characterizations of the Urate Transporter, GLUT9, and Its Potent Inhibitors by Patch-Clamp Technique

Protective effects of S‐carvedilol on doxorubicin‐induced damages to human umbilical vein endothelial cells and rats

Novel Oxidative Stress Biomarkers with Risk Prognosis Values in Heart Failure

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