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Journal of Pharmaceutical Analysis Oct 2018Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by...
Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by hyphenated ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Indapamide-d3, perindopril-d4 and perindoprilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C column (4.6 mm × 100 mm, 2.4 µm) for indapamide and perindopril simultaneously following a protein precipitation pretreatment of the biosamples. The separation of perindoprilat was achieved independently on a phenomenex PFP column (4.6 mm × 150 mm, 5 µm). All the analytes were quantitated with positive electrospray ionization and multiple reactions monitoring mode. The assay exhibited a linear range of 1-250 ng/mL for indapamide, 0.4-100 ng/mL for perindopril and 0.2-20 ng/mL for perindoprilat. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to the pharmacokinetic study of perindopril tert-butylamine/indapamide compound tablets in Chinese healthy volunteers and the comparative pharmacokinetic study between plasma and whole blood.
PubMed: 30345148
DOI: 10.1016/j.jpha.2018.05.004 -
Naunyn-Schmiedeberg's Archives of... Jun 2016We aim to evaluate the protective role of the central angiotensin-converting enzyme (ACE) inhibitor perindopril, compared with the standard reactive oxygen species (ROS)... (Comparative Study)
Comparative Study
Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress.
We aim to evaluate the protective role of the central angiotensin-converting enzyme (ACE) inhibitor perindopril, compared with the standard reactive oxygen species (ROS) scavenger tempol, against lipopolysaccharide (LPS)-induced cognition impairment and amyloidogenesis in a simulation to Alzheimer's disease (AD). Mice were allocated into a control group, an LPS control group (0.8 mg/kg, i.p., once), a tempol (100 mg/kg/day, p.o., 7 days) treatment group, and two perindopril (0.5 and 1 mg/kg/day, p.o., 7 days) treatment groups. A behavioral study was conducted to evaluate spatial and nonspatial memory in mice, followed by a biochemical study involving assessment of brain levels of Aβ and BDNF as Alzheimer and neuroplasticity markers; tumor necrosis factor-alpha (TNF-α), nitric oxide end-products (NOx), neuronal nitric oxide synthase (nNOS), and inducible nitric oxide synthase (iNOS) as inflammatory markers; and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using both routine and special staining. Tempol and perindopril improved spatial and nonspatial memory in mice without affecting locomotor activity; decreased brain Aβ deposition and BDNF depletion; decreased brain TNF-α, NOx, nNOS, iNOS, MDA, and NT levels; and increased brain SOD and GSH contents, parallel to confirmatory histopathological findings. Tempol and perindopril may be promising agents against AD progression via suppression of Aβ deposition and BDNF decline, suppression of TNF-α production, support of brain antioxidant status, and amelioration of oxido-nitrosative stress and NT production.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Behavior, Animal; Biomarkers; Brain; Brain-Derived Neurotrophic Factor; Cognition; Cognition Disorders; Cyclic N-Oxides; Disease Models, Animal; Inflammation Mediators; Lipopolysaccharides; Male; Maze Learning; Mice, Inbred BALB C; Motor Activity; Neuroprotective Agents; Oxidative Stress; Perindopril; Reactive Nitrogen Species; Recognition, Psychology; Spatial Memory; Spin Labels; Time Factors
PubMed: 27026404
DOI: 10.1007/s00210-016-1234-6 -
Frontiers in Pharmacology 2021Wear particles may induce osteoclast formation and osteoblast inhibition that lead to periprosthetic osteolysis (PPOL) and subsequent aseptic loosening, which is the...
Wear particles may induce osteoclast formation and osteoblast inhibition that lead to periprosthetic osteolysis (PPOL) and subsequent aseptic loosening, which is the primary reason for total joint arthroplasty failure. Local bone renin-angiotensin system (RAS) has been found to participate in the pathogenic process of various bone-related diseases via promoting bone resorption and inhibiting bone formation. However, it remains unclear whether and how local bone RAS participates in wear-particle-induced PPOL. In this study, we investigated the potential role of RAS in titanium (Ti) particle-induced osteolysis and osteoclast and osteoblast differentiation . We found that the expressions of AT1R, AT2R and ACE in the interface membrane from patients with PPOL and in calvarial tissues from a murine model of Ti-particle-induced osteolysis were up-regulated, but the increase of ACE in the calvarial tissues was abrogated by perindopril. Moreover, perindopril mitigated the Ti-particle-induced osteolysis in the murine model by suppressing bone resorption and increasing bone formation. We also observed in RAW264.7 macrophages that Ang II promoted but perindopril suppressed Ti-particle-induced osteoclastogenesis, osteoclast-mediated bone resorption and expression of osteoclast-related genes. Meanwhile, Ang II enhanced but perindopril repressed Ti-particle-induced suppression of osteogenic differentiation and expression of osteoblast-specific genes in mouse bone marrow mesenchymal stem cells (BMSCs). In addition, local bone RAS promoted Ti-particle-induced osteolysis by increasing bone resorption and decreasing bone formation through modulating the RANKL/RANK and Wnt/β-catenin pathways. Taken together, we suggest that inhibition of RAS may be a potential approach to the treatment of wear-particle-induced PPOL.
PubMed: 34248634
DOI: 10.3389/fphar.2021.684375 -
Georgian Medical News Oct 2023Drug-induced Nitrosogenesis/Carcinogenesis turns out to be a ubiquitous, pervasive, large-scale, poorly controllable concept for the academic community, which underlies...
METASTATIC NODULAR MELANOMA DEVELOPING ON NEVUS SPILUS DURING INTAKE OF BETA BLOCKERS (BISOPROLOL/NEBIVOLOL) AND ACE INHIBITORS (PERINDOPRIL). POTENTIAL LINKS TО THE DRUG RELATED NITROSOGENESIS/CARCINOGENESIS, DUNNING-KRUGER EFFECT AND GENETIC WEAPONS OF THE NEW GENERATION.
Drug-induced Nitrosogenesis/Carcinogenesis turns out to be a ubiquitous, pervasive, large-scale, poorly controllable concept for the academic community, which underlies the long-term, permanent modification of the human genome by contact with nitrosamines/NDSRIs, which ultimately leads to the generation of diverse cancers, but also melanoma in particular. The discovery of a (currently) unclassifiable number of nitroso derivatives/genome modifiers in the most commonly distributed drugs worldwide (in about 300 preparations according to the FDA/includes beta blockers/bisoprolol/nebivolol and ACE inhibitors/perindopril), their forced tolerability, attributed as a necessity or lack of alternative also to the present (but also to future periods), and their proven carcinogenicity (already 70 years ago), suggest a kind of creepy form of experiment to which public health is subjected worldwide. The creation of a universal nitroso-comfort of pharmaceutical companies and the regulation of a permanent intake of carcinogens in drugs for years to come, but also decades back, suggest possible cartel agreements between the regulation/distribution unit and that of production cycles. These "agreements" are becoming increasingly evident and in all likelihood position nitrosogenesis from a until recently unknown element, to a pathogenetic factor of paramount importance. Melanoma could be viewed precisely as the controlled end gene-modified product of drug-mediated nitrosogenesis/carcinogenesis, proven to be a locoregional (but not only) phenomenon hundreds if not thousands of times. The dilemma stays: Are the nitrosamines in drugs genetic weapons, ethnic bioweapons for silent war ? The nitrosogenesis concerning melanoma leads to the logical conclusion that cancer is in fact a largely controlled set event or, according to others, a forced necessity of evolutionary globalization processes to purge the population in certain regions. In favor of this statement indicative are namely: 1) lack of regulatory control/results of such conducted, 2) complete information veil for the end user regarding contamination with carcinogens/nitrosamines in certain batches or all batches of drugs, 3) misinformation and lack of transparency regarding the concept of nitrosogenesis also for the academic community, as well as 4) the impunity to pharmaceutical conglomerates after criminal negligence/controlled criminogenicity proven thousands of times by the FDA/EMA leading to regulatory controlled drug mediated genocide of the human population in certain areas on a daily basis. And most important of all: 5) the lack of refusal to eliminate these drugs, i.e. - the imposition of forced tolerance at any cost. It is extremely unfortunate that the mentioned and identified grotesque/situation, its tolerance on a global scale, lead to a misjudgement of the significance of real tumor inducers within the global health map//statistics as well as melanoma. The focus of prevention is being displaced, while the incidence of cancer in general and that of melanoma is skyrocketing. Nitrosamines could be defined as the newest, modern, until recently invisible and unknown, but -controllable form of genetic weapon to modify the human genome. Because of these very facts, the likelihood that clinicians and the academic community are in the frozen and permanent state of the Dunning-Kruger effect is very real. Certain globalization regulatory elements create problems and assignments that must be solved ˝competently˝ by incompetent, fully regulatable compartments. As their state of competence depends again and entirely on ˝their incompetence˝. Until now. After the formalization of the concept of Nitrosogenesis (as a form of genetic weapon) and melanoma for example, but not only, it remains to be seen whether universal incompetence will become a guarantee of competence and the survival. Or- will it remain again at the level of globalized, criminally conditioned, appointed and regulated from above "competent incompetence". The dilemmas to regulators and manufacturers remain open : Is it competent to take drugs that contain carcinogens/nitrosamines? Is it competent for this issue to continue for decades with impunity? Is it competent for regulators not to inform consumers about the presence of carcinogens/genome modifiers in medicines for decades? Is it competent for certain regions to be affected by nitrosamine contamination and not others? Is it competent not to reflect this in regional and global health bulletins on side effects? Is it competent to make thousands of times the profits from the modified genetic map business, regulated and legally initiated through the intake of carcinogens? Is it competent to have the concentration of carcinogens within polymedication exceeding many times the daily allowable doses of carcinogens and have no solution for this? Is it competent, when the intake of nitrosamines in medicines is associated with the generation of melanomas and heterogeneous cancers- to have no alternative to this or when one is available- to conceal it skillfully? Is it competent to determine carcinogenic activity based on mutagenic tests? Is it competent to be polyincompetent within a framework of mass (in)competence? We report systemically administered drugs for the treatment of high blood pressure from the group of beta blockers (bisoprolol/nebivolol) and ACE inhibitors (perindopril) that have been identified by regulators in the face of FDA as hypothetically contaminated with nitrosamines/NDSRIs with a carcinogenic potency between 4 and 5, respectively. Within this cumulative intake, (which according to the regulators was not at risk of developing cancerous forms), similar to other cases in the world literature, the patient developed a relatively short-term, metastatic nevus spilus-based nodular melanoma. The paper analyses not only the role of nitrosogenesis, but also that of two pregnancies and painful sunburns as potential cofactors for melanoma genesis. Academic attention is drawn to the potential impact of drug-mediated nitrosogenesis/carcinogenesis. Nitrosamines in the framework of polycontamination and polymedication could also be identified as one of the most effective, until recently unknown, modern generation genetic weapons for modifying the human genome and controlling cancer. Moreover, they could be controllably applied and skillfully targeted. At least until now. The officialization of carcinogens in more than 250 of the most common drugs and the clinico-pathological correlations concerning the development of cancer/melanoma in poorly controlled geographical regions represent a kind of in vivo prospective study to determine precisely the real carcinogenic role of nitrosamines to date.
Topics: Humans; Melanoma; Perindopril; Bisoprolol; Nebivolol; Angiotensin-Converting Enzyme Inhibitors; Prospective Studies; Skin Neoplasms; Carcinogens; Nitrosamines; Carcinogenesis; Adrenergic beta-Antagonists; Pharmaceutical Preparations; Nevus
PubMed: 38096536
DOI: No ID Found -
Frontiers in Cardiovascular Medicine 2022β-blockers have been recommended for patients with heart failure (HF) and atrial fibrillation (AF), but studies have shown that β-blockers do not reduce all-cause...
BACKGROUND
β-blockers have been recommended for patients with heart failure (HF) and atrial fibrillation (AF), but studies have shown that β-blockers do not reduce all-cause mortality or cardiovascular mortality in patients with HF and AF.
OBJECTIVE
To investigate the difference in efficacy between oral amiodarone and metoprolol succinate for patients with HF with reduced ejection fraction (HFrEF) and persistent atrial fibrillation (pAF) with rapid ventricular response (RVR).
METHODS
Patients with HFrEF complicated with pAF with RVR treated in the People's Hospital of Chongqing Hechuan between March 2018 and March 2019 were enrolled in this prospective observational study. The primary outcomes were cardiovascular mortality and the first hospitalization for HF rate. The secondary outcomes were type B pro-brain natriuretic peptide (NT-proBNP) before/after treatment, left ventricular ejection fraction (LVEF) before/after treatment, average heart rate (AhR), and the rate of sinus rhythm after 1 year of follow-up.
RESULTS
A total of 242 patients with HFrEF complicated with pAF with RVR were enrolled and divided into amiodarone + perindopril + spironolactone+ routine drug (amiodarone group, = 121) and metoprolol succinate + perindopril + spironolactone +routine drug (metoprolol succinate group, = 121) according to their treatment strategy. Cardiovascular mortality (4.9 vs. 12.4%, HR: 2.500, 95%CI: 1.002-6.237, = 0.040) and first hospitalization for HF (52.9 vs. 67.8%, HR: 1.281, 95%CI: 1.033-1.589, = 0.024) were significantly lower in the amiodarone group than in the metoprolol group. The mean ventricular rate in the amiodarone group was significantly lower than in the metoprolol group (64.5 ± 3.2 vs. 72.4 ± 4.2, < 0.001). After 1 year of follow-up, the sinus rhythm rate was significantly higher in the amiodarone group than in the metoprolol group (38.8 vs. 7.4%, HR: 0.191, 95%CI: 0.098-0.374, < 0.001). The difference in proBNP (3,914.88 vs. 2,558.07, < 0.001) and LVEF (-6.89 vs. -0.98, < 0.001) before and after treatment was significantly higher in the amiodarone group than in the metoprolol group.
CONCLUSION
In conclusion, in this prospective observational study, the amiodarone group had lower risk of cardiovascular death and the first hospitalization for HF than metoprolol in HFrEF and persistent atrial fibrillation (pAF) with RVR. The mechanism may be related to improved cardiac function, rhythm control and ventricular rate control.
REGISTRATION NUMBER
ChiCTR2200057816; Registered 7 March 2022-Retrospectively registered: http://www.medresman.org.cn/pub/cn/proj/projectshshow.aspx?proj=4222.
PubMed: 36698920
DOI: 10.3389/fcvm.2022.1029012 -
Life Sciences Dec 2015The aim of this work was to evaluate the effects of treatment of hypertension on the autoantibodies to apolipoprotein B-derived peptides (anti-ApoB-D peptide Abs)... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
The aim of this work was to evaluate the effects of treatment of hypertension on the autoantibodies to apolipoprotein B-derived peptides (anti-ApoB-D peptide Abs) response, inflammation markers and vascular function.
MAIN METHODS
Eighty-eight patients with hypertension (stage 1 or 2) were recruited and advised to receive perindopril (4mg), hydrochlorothiazide (25mg), or indapamide (1.5mg) for 12weeks in a blinded fashion. Office and 24-h ambulatory blood pressure monitoring (24h ABPM), flow-mediated dilatation (FMD), nitrate-induced dilatation (NID), titers of IgG and IgM anti-ApoB-D peptide Abs, hsCRP, and interleukins (IL-8 and IL-10) were evaluated at baseline and 12weeks after therapies.
KEY FINDINGS
All treatments reduced office BP, and improved FMD (P<0.05 vs. baseline). The NID was improved only in the perindopril arm (P<0.05 vs. baseline). The 24h-ABPM was reduced with perindopril and hydrochlorothiazide therapies (P<0.05 vs. baseline), but not with indapamide, and this effect was followed by increase in titers of IgM Anti-ApoB-D peptide Abs (P<0.05 vs. baseline), without modifications in titers IgG Anti-ApoB-D peptide Abs and interleukins. Multivariable regression analysis has shown that change in the titers of IgM anti-ApoB-D peptide was associated with the changes in FMD (β -0.347; P<0.05).
SIGNIFICANCE
These findings shed light to a possible modulator effect of the antihypertensive therapy on the natural immunity responses and vascular function.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Female; Humans; Hydrochlorothiazide; Hypertension; Immunity, Innate; Indapamide; Male; Middle Aged; Perindopril; Single-Blind Method
PubMed: 26514303
DOI: 10.1016/j.lfs.2015.10.030 -
Analytical Chemistry May 2022The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear....
The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1.617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.
Topics: Angiotensin-Converting Enzyme 2; Antibodies, Neutralizing; COVID-19; Humans; Immunoglobulin Isotypes; Protein Array Analysis
PubMed: 35442638
DOI: 10.1021/acs.analchem.1c05567 -
Nutrition, Metabolism, and... Sep 2022To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on...
Impact of simultaneous management of hypertension and hypercholesterolemia with ACE inhibitors and statins on cardiovascular outcomes in the Brisighella Heart Study: A 8-year follow-up.
BACKGROUND AND AIMS
To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes.
METHODS AND RESULTS
We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05).
CONCLUSION
Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.
Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atorvastatin; Blood Pressure; Calcium; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Perindopril
PubMed: 35843791
DOI: 10.1016/j.numecd.2022.06.017 -
Neurology. Clinical Practice Oct 2021To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy...
OBJECTIVE
To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy (DMD) compared with placebo.
METHODS
This multicenter, parallel group, 1:1 patient randomized, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of left ventricular (LV) function, electrocardiogram, and adverse event reporting were performed 6 monthly. The primary outcome was change in ejection fraction between arms after 36 months. The study was approved by the National Research Ethics Service Committee East Midlands-Derby.
RESULTS
Eighty-five boys were recruited (76% on steroid therapy) and randomized to combination heart drugs or matched placebo. Group change in left ventricular ejection fraction (LVEF%) at 36 months from baseline was -2.2% ± 6.0% and -2.9% ± 6.1% in active and placebo arms (adjusted mean difference: -2.1, 95% CI -5.2 to 1.1). There was no difference between treatment arms over repeated assessments (analysis of variance) up to 36 months (trial arms = 0.53); arm-over-time ( = 0.44). Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function. Secondary outcomes did not differ between arms either. Thirty-six serious adverse events occurred none due to cardiac events or trial medication.
CONCLUSIONS
Combination therapy was well tolerated. Consistent with the previous prophylactic perindopril heart study, there was no evidence of group benefit after 36-month treatment.
CLASSIFICATION OF EVIDENCE
This study provides Class I evidence that combination perindopril-bisoprolol therapy was well tolerated but did not change decline in LVEF significantly in boys with DMD.
PubMed: 34840880
DOI: 10.1212/CPJ.0000000000001023 -
Cardiology Research and Practice 2022Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are...
BACKGROUND
Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are challenging in humans. We applied a noninvasive forearm skin measurement of the 460-nm fluorescence specific for the reduced form of nicotinamide adenine dinucleotide (NADH) to study the 6-week effects of four different antihypertensive medications on mitochondrial function using the Flow-Mediated Skin Fluorescence (FMSF).
METHODS
In a prospective open-label study, we compared the long-term effects of a 6-week treatment with either amlodipine (5 mg), perindopril (5 mg), nebivolol (5 mg), or metoprolol (50 mg) on the dynamic flow-mediated changes in the skin NADH content in 76 patients (29 women) with untreated primary arterial hypertension (HA). Patients underwent 24-hour ambulatory blood pressure monitoring. To study mitochondrial function, the FMSF was measured at rest, during 100-second ischemia and postischemic reperfusion. The control group consisted of 18 healthy people (7 women).
RESULTS
There were no significant differences in the FMSF parameters between the control and the study group before medication. After the 6-week treatment, all drugs similarly reduced blood pressure. Neither amlodipine, perindopril, nor nebivolol changed the flow-mediated 460-nm skin fluorescence significantly. However, metoprolol raised this fluorescence at rest, during ischemia and reperfusion ( at most <0.05), indicating an increase in the total NADH skin content.
CONCLUSION
Amlodipine, perindopril, and nebivolol appear neutral for the skin NADH content during the 6-week antihypertensive treatment. Similar treatment with metoprolol increased skin NADH at rest, during ischemia and reperfusion, probably due to an effect on microcirculation and altered mitochondrial function. Explanation of the potential mechanisms behind metoprolol influence on the skin NADH metabolism requires further investigation.
PubMed: 35402043
DOI: 10.1155/2022/6159883