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1.
Sci Rep ; 14(1): 12625, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824234

ABSTRACT

Treatment intensification is essential to ensure guideline targets are attained in diabetes patients. The failure to intensify treatment when the targets are not achieved is therapeutic inertia. This study aimed to determine the proportions and factors associated with treatment intensification and therapeutic inertia of antihypertensive therapy in type 2 diabetes patients with uncontrolled hypertension in Malaysia. A retrospective cohort analysis was conducted utilising registry data. Diabetes hypertensive patients with uncontrolled baseline systolic or diastolic blood pressure were included. Treatment intensification was the increase in the number of antihypertensive agents from the index treatment. Therapeutic inertia was the absence of treatment intensification when the second blood pressure reading was still uncontrolled. About 6956 patients were followed up over 2.5 ± 1.1 person-years. Treatment intensification was observed in 29.8% of patients, while 38.6% had therapeutic inertia. Chinese, Indian, and 'others' ethnic groups, retinopathy, more antihypertensive agents, and higher systolic blood pressure were associated with therapeutic inertia. Underweight, overweight patients and those with dyslipidaemia had lower risks for therapeutic inertia. The results indicate suboptimal quality of care in public health clinics in Malaysia. Further studies are needed to determine the underlying causes to formulate precise interventions to tackle the problem in Malaysia.


Subject(s)
Antihypertensive Agents , Blood Pressure , Diabetes Mellitus, Type 2 , Hypertension , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Hypertension/drug therapy , Antihypertensive Agents/therapeutic use , Female , Male , Middle Aged , Blood Pressure/drug effects , Retrospective Studies , Malaysia , Aged
2.
J Hypertens ; 42(7): 1184-1196, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38690916

ABSTRACT

PURPOSE: Compared with monotherapy, combination therapy with multiple antihypertensive drugs has demonstrated superior efficacy in the management of hypertension. The aim of this study was to explore the efficacy of multitarget combined vaccines in achieving simultaneous antihypertensive and target organ protection effects. METHODS: Our team has developed ATRQß-001 and ADRQß-004 vaccines targeting Ang II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR), respectively. In NG-nitroarginine methyl ester ( l -NAME) + abilities spontaneously hypertensive rats (SHRs) model, SHRs were simultaneously inoculated with ATRQß-001 and ADRQß-004 vaccines. Histological and biochemical analyses were performed to evaluate the antihypertensive effects and target organ protection of the ATRQß-001 and ADRQß-004 combined vaccines in comparison with those of the single vaccine. RESULTS: Both ATRQß-001 and ADRQß-004 vaccines induced robust antibody production, resulting in persistent high antibody titers in rats. Notably, the combined administration of both vaccines significantly decreased SBP in SHRs compared with treatment with a single vaccine, both before and after l -NAME administration. Furthermore, the combined vaccine regimen demonstrated superior efficacy in protecting against vascular remodeling, myocardial hypertrophy and fibrosis, and kidney injury in SHRs. Mechanistically, the combined vaccines exhibited significantly downregulated the expression of angiotensin II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR). Importantly, no apparent immune-related adverse effects were observed in animals immunized with the combined vaccines. CONCLUSION: Preliminary findings from this investigation suggest that co-administration of the novel ATRQß-001 and ADRQß-004 vaccines holds potential as a groundbreaking therapeutic strategy for managing hypertension.


Subject(s)
Hypertension , Rats, Inbred SHR , Receptor, Angiotensin, Type 1 , Receptors, Adrenergic, alpha-1 , Animals , Receptor, Angiotensin, Type 1/immunology , Rats , Male , Vaccines, Combined/immunology , NG-Nitroarginine Methyl Ester/pharmacology , Blood Pressure/drug effects
4.
J Feline Med Surg ; 26(5): 1098612X241240326, 2024 May.
Article in English | MEDLINE | ID: mdl-38770706

ABSTRACT

OBJECTIVES: The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD). METHODS: A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location. RESULTS: After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; P = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; P = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; P = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups). CONCLUSIONS AND RELEVANCE: Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.


Subject(s)
Blood Pressure , Cat Diseases , Cross-Over Studies , Gabapentin , Renal Insufficiency, Chronic , Animals , Cats , Gabapentin/administration & dosage , Gabapentin/pharmacology , Gabapentin/therapeutic use , Cat Diseases/drug therapy , Renal Insufficiency, Chronic/veterinary , Renal Insufficiency, Chronic/drug therapy , Blood Pressure/drug effects , Male , Female
5.
J Am Heart Assoc ; 13(10): e031695, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38752519

ABSTRACT

BACKGROUND: We examined the association of multilevel social determinants of health with incident apparent treatment-resistant hypertension (aTRH). METHODS AND RESULTS: We analyzed data from 2774 White and 2257 Black US adults from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study taking antihypertensive medication without aTRH at baseline to estimate the association of social determinants of health with incident aTRH. Selection of social determinants of health was guided by the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access. Blood pressure (BP) was measured during study visits, and antihypertensive medication classes were identified through a pill bottle review. Incident aTRH was defined as (1) systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg for those with diabetes or chronic kidney disease while taking ≥3 classes of antihypertensive medication or (2) taking ≥4 classes of antihypertensive medication regardless of BP level, at the follow-up visit. Over a median 9.5 years of follow-up, 15.9% of White and 24.0% of Black adults developed aTRH. A percent of the excess aTRH risk among Black versus White adults was mediated by low education (14.2%), low income (16.0%), not seeing a friend or relative in the past month (8.1%), not having someone to care for them if ill or disabled (7.6%), lack of health insurance (10.6%), living in a disadvantaged neighborhood (18.0%), and living in states with poor public health infrastructure (6.0%). CONCLUSIONS: Part of the association between race and incident aTRH risk was mediated by social determinants of health.


Subject(s)
Antihypertensive Agents , Black or African American , Hypertension , Social Determinants of Health , White People , Humans , Social Determinants of Health/ethnology , Male , United States/epidemiology , Female , Hypertension/drug therapy , Hypertension/ethnology , Hypertension/epidemiology , Hypertension/physiopathology , Middle Aged , Antihypertensive Agents/therapeutic use , Black or African American/statistics & numerical data , White People/statistics & numerical data , Aged , Incidence , Risk Factors , Blood Pressure/drug effects , Drug Resistance , Health Status Disparities , Educational Status , Health Services Accessibility
6.
AAPS PharmSciTech ; 25(5): 115, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755324

ABSTRACT

More than 1 billion people worldwide suffer from hypertension; therefore, hypertension management has been categorized as a global health priority. Losartan potassium (LP) is an antihypertensive drug with a limited oral bioavailability of about 33% since it undergoes the initial metabolic cycle. Thus, nasal administration is a unique route to overcome first-pass metabolism. The investigation focused on the potential effects of LP-loaded spanlastic vesicles (SNVs) on LP pharmacodynamics and pharmacokinetic parameters, utilizing a thin-film hydration methodology established on a 3122 full factorial design. Entrapment efficiency (EE%) ranged from 39.8 ± 3.87.8 to 83.8 ± 2.92% for LP-SNVs. Vesicle size (VS) varied from 205.5 ± 6.5.10 to 445.1 ± 13.52 nm, and the percentage of LP released after 8 h (Q8h) ranged from 30.8 ± 3.10 to 68.8 ± 1.45%. LP permeated through the nasal mucosa during 24 h and flocculated from 194.1 ± 4.90 to 435.3 ± 13.53 µg/cm2. After twenty-four hours, the optimal LP-SNVs in-situ gel showed 2.35 times more permeation through the nasal mucosa than the LP solution. It also lowered systolic blood pressure, so it is thought to be better than the reference formulation in terms of pharmacodynamics. The pharmacokinetics studies demonstrated that the intranasal LP-SNVs gel boosted its bioavailability approximately 6.36 times compared to the oral LP solution. Our research showed that intranasal LP-SNVs could be a good nanoplatform because they are well-tolerated and have possible pharmacokinetics and pharmacodynamics.


Subject(s)
Antihypertensive Agents , Gels , Hypertension , Losartan , Losartan/pharmacokinetics , Losartan/administration & dosage , Losartan/pharmacology , Antihypertensive Agents/pharmacokinetics , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/pharmacology , Animals , Hypertension/drug therapy , Male , Rats , Biological Availability , Administration, Intranasal , Nanoparticles/chemistry , Nasal Mucosa/metabolism , Nasal Mucosa/drug effects , Particle Size , Angiotensin II/pharmacokinetics , Angiotensin II/administration & dosage , Angiotensin II/pharmacology , Blood Pressure/drug effects , Rats, Wistar , Chemistry, Pharmaceutical/methods
7.
Nat Commun ; 15(1): 3962, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730247

ABSTRACT

Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits.


Subject(s)
Chalcones , Adult , Aged , Female , Humans , Male , Middle Aged , Adiponectin/metabolism , Adiponectin/blood , Blood Glucose/metabolism , Blood Glucose/drug effects , Blood Pressure/drug effects , Cardiovascular Diseases/drug therapy , Chalcones/therapeutic use , Chalcones/pharmacology , Fatty Liver/drug therapy , Fatty Liver/metabolism , Insulin Resistance , Lipid Metabolism/drug effects , Liver/drug effects , Liver/pathology , Liver/metabolism , Peroxisome Proliferator-Activated Receptors/agonists , Peroxisome Proliferator-Activated Receptors/metabolism , Propionates , Triglycerides/blood , Triglycerides/metabolism
8.
Med ; 5(5): 383-385, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38733971

ABSTRACT

Hypertension is a modifiable risk factor for cardiovascular disease, the leading cause of death worldwide, yet most US adults with hypertension do not meet goal blood pressure. KARDIA-1 demonstrates the efficacy of zilebesiran, a subcutaneously administered small interfering RNA, for lowering blood pressure, presenting a novel treatment option for this deadly disease.1.


Subject(s)
Hypertension , RNA, Small Interfering , Hypertension/genetics , Humans , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/therapeutic use , Blood Pressure/drug effects
9.
Bull Exp Biol Med ; 176(5): 543-547, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38717566

ABSTRACT

We studied the dynamics of the main hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with visceral obesity and chemically induced colitis (CIC) against the background of probiotic therapy. Systolic BP, HR, and body temperature were recorded over 36 days using a wireless telemetry system. During 8 days (3 days before CIC induction and until the end of the experiment) the animals were intragastrically administered a probiotic based on Lactobacillus delbrueckii D5 strain. At baseline, systolic BP was significantly higher in the SHR group, while HR and body temperature did not differ in SHR and WKY rats. On day 8 after CIC induction, systolic BP, HR, and body temperature in SHR were significantly increased in comparison with the initial values. In the group of WKY rats, all indices at the end of the experiment remained at the initial levels. Probiotic therapy in SHR, in contrast to WKY rats, did not lead to normalization of body temperature and hemodynamic disorders resulting from CIC.


Subject(s)
Body Temperature , Colitis , Hemodynamics , Probiotics , Rats, Inbred SHR , Rats, Inbred WKY , Animals , Probiotics/pharmacology , Probiotics/administration & dosage , Rats , Male , Colitis/chemically induced , Colitis/physiopathology , Colitis/microbiology , Hemodynamics/drug effects , Body Temperature/drug effects , Blood Pressure/drug effects , Blood Pressure/physiology , Heart Rate/drug effects , Lactobacillus delbrueckii , Obesity/physiopathology , Obesity, Abdominal/physiopathology , Obesity, Abdominal/chemically induced
10.
Kardiologiia ; 64(4): 61-70, 2024 Apr 30.
Article in Russian | MEDLINE | ID: mdl-38742517

ABSTRACT

The article discusses current issues of the treatment of arterial hypertension. According to presented data, so-called therapeutic nihilism is becoming one of the main barriers to achieving target blood pressure (BP). This nihilism is that despite evidence of the effectiveness of achieving lower BP values, practitioners do not intensify antihypertensive therapy sufficiently to achieve such values. The article specially addresses new criteria for the effectiveness of antihypertensive therapy, which reflect the therapy sustainability. The most commonly used indicator is the duration of the period, during which systolic BP remains in the therapeutic range. The prognostic significance of such indicators is discussed. In these conditions, it is very important to use the most effective antihypertensive drugs for initial antihypertensive therapy, including as a part of combination therapy. This tactic provides more frequent achievement of BP goals without the need for dose adjustment. In this regard, a systematic review was performed, which included sufficiently large randomized studies of the antihypertensive effectiveness of azilsartan medoxomil. This systematic review will provide comprehensive information on a possible role of using the angiotensin II receptor blocker azilsartan as a basic drug for the treatment of a wide range of patients with high BP. Most of the studies included in the systematic review assessed the effectiveness of combination therapy including azilsartan.


Subject(s)
Antihypertensive Agents , Benzimidazoles , Blood Pressure , Hypertension , Oxadiazoles , Humans , Oxadiazoles/therapeutic use , Oxadiazoles/pharmacology , Hypertension/drug therapy , Hypertension/physiopathology , Antihypertensive Agents/therapeutic use , Benzimidazoles/therapeutic use , Benzimidazoles/pharmacology , Blood Pressure/drug effects , Blood Pressure/physiology , Drug Therapy, Combination
13.
J Prev Alzheimers Dis ; 11(3): 672-683, 2024.
Article in English | MEDLINE | ID: mdl-38706283

ABSTRACT

BACKGROUND: We aimed to explore whether the relationships of blood pressures (BPs) with Alzheimer's disease (AD) endophenotypes varied by usage of antihypertensive drugs (AHDs). METHODS: A total of 765 non-demented older adults (mean age: 74.4 years; female: 43.1%) with a self-reported history of hypertension were followed for 6 years. Multiple linear regression and linear-mixed effect models were used to investigate the interaction effects of five categories of AHDs (angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARBs], ß-blocker, calcium channel blockers [CCB], diuretic) with BPs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) on AD core pathology and neurodegenerative markers. RESULTS: After Bonferroni correction, significant interaction effects of BPs with AHDs were observed. Elevated SBP or PP in late-life was associated with higher levels of cerebral Aß burden (diuretic alone/ß-blocker × SBP), higher levels of CSF tau proteins (diuretic × SBP/PP, ARBs/CCB × SBP), and lower volume of entorhinal region (ß-blocker × SBP, diuretic × PP) only among hypertensive patients who received no anti-hypertensive treatments, while these associations became compromised or null for users of specific AHDs except for ACEI. Compared to taking other classes of AHDs, elevated SBP in late-life was associated with lower cerebral Aß burden in diuretic users (padjusted = 0.08) and was associated with higher CSF tau proteins in ACEI alone users (padjusted = 0.03). Longitudinal data validated the above-mentioned interaction effects on changes of cerebral Aß burden (padjusted < 0.05), CSF tau proteins (padjusted < 0.10), and brain atrophy (padjusted < 0.05). CONCLUSIONS: The relationships of late-life BP with AD pathology and neurodegeneration could be modified by anti-hypertensive treatments and varied by AHD classification. These findings provide preliminary evidence for tailored BP management strategy for preventing AD among late-life hypertensive adults.


Subject(s)
Alzheimer Disease , Antihypertensive Agents , Blood Pressure , Hypertension , Humans , Aged , Female , Male , Hypertension/drug therapy , Alzheimer Disease/drug therapy , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Blood Pressure/physiology , tau Proteins/cerebrospinal fluid , tau Proteins/metabolism , Biomarkers/cerebrospinal fluid , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Calcium Channel Blockers/therapeutic use
14.
J Trace Elem Med Biol ; 84: 127460, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38703538

ABSTRACT

BACKGROUND: Exposure to metals during pregnancy can potentially influence blood pressure (BP) in children, but few studies have examined the mixed effects of prenatal metal exposure on childhood BP. We aimed to assess the individual and combined effects of prenatal metal and metalloid exposure on BP in preschool children. METHODS: A total of 217 mother-child pairs were selected from the Zhuang Birth Cohort in Guangxi, China. The maternal plasma concentrations of 20 metals [e.g. lead (Pb), rubidium (Rb), cesium (Cs), and zinc (Zn)] in early pregnancy were measured by inductively coupled plasmamass spectrometry. Childhood BP was measured in August 2021. The effects of prenatal metal exposure on childhood BP were explored by generalized linear models, restricted cubic spline and Bayesian kernel machine regression (BKMR) models. RESULTS: In total children, each unit increase in the log10-transformed maternal Rb concentration was associated with a 10.82-mmHg decrease (95% CI: -19.40, -2.24) in childhood diastolic BP (DBP), and each unit increase in the log10-transformed maternal Cs and Zn concentrations was associated with a 9.67-mmHg (95% CI: -16.72, -2.61) and 4.37-mmHg (95% CI: -8.68, -0.062) decrease in childhood pulse pressure (PP), respectively. The log10-transformed Rb and Cs concentrations were linearly related to DBP (P nonlinear=0.603) and PP (P nonlinear=0.962), respectively. Furthermore, an inverse association was observed between the log10-transformed Cs concentration and PP (ß =-12.18; 95% CI: -22.82, -1.54) in girls, and between the log10-transformed Rb concentration and DBP (ß =-12.54; 95% CI: -23.87, -1.21) in boys, while there was an increasing association between the log10-transformed Pb concentration and DBP there was an increasing in boys (ß =6.06; 95% CI: 0.36, 11.77). Additionally, a U-shaped relationship was observed between the log10-transformed Pb concentration and SBP (P nonlinear=0.015) and DBP (P nonlinear=0.041) in boys. Although there was no statistically signiffcant difference, there was an inverse trend in the combined effect of maternal metal mixture exposure on childhood BP among both the total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to both individual and mixtures of metals and metalloids influences BP in preschool children, potentially leading to nonlinear and sex-specific effects.


Subject(s)
Blood Pressure , Maternal Exposure , Metalloids , Metals , Humans , Female , Blood Pressure/drug effects , Child, Preschool , Pregnancy , Maternal Exposure/adverse effects , Male , Metalloids/blood , Metals/blood , Adult , Prenatal Exposure Delayed Effects/chemically induced , Lead/blood , China , Zinc/blood , Bayes Theorem
15.
Sci Rep ; 14(1): 11671, 2024 05 22.
Article in English | MEDLINE | ID: mdl-38778051

ABSTRACT

This study delves into the effectiveness of combining remimazolam with low-dose propofol in pediatric fiberoptic bronchoscopy. Ninety children scheduled for fiberoptic bronchoscopy in our hospital were enrolled as research participants. Based on the intraoperative anesthetic drug regimen, the children were divided into three groups: group R (remimazolam 0.2-0.4 mg/kg), group P (propofol 1-3 mg/kg), and group RP (remimazolam0.2 mg/kg, propofol 0.5 mg/kg). Immediately post-anesthesia, group P exhibited lower blood pressure and heart rate (HR) compared to both group R and group RP (P < 0.05). As bronchoscope approached the glottis and epiglottis, group P continued to display lower blood pressure and HR compared to group R and group RP (P < 0.05). During lavage, group P maintained lower blood pressure and HR compared to both the R and RP groups (P < 0.05). Immediately post-anesthesia, group P demonstrated lower SpO2 compared to the R and RP groups (P < 0.05).During lavage, group P maintained lower SpO2 than group R and group RP (P < 0.05). In comparison with group R and group PR, group P showed shortened induction and recovery times (P < 0.05). The one-time entry success rate into the microscope was higher in group R than in group P, with the RP group showing an intermediate decreased (P < 0.05). Moreover, the cough score in R group was higher than in the P and RP groups (P < 0.05). Furthermore, the satisfaction rates of the RP group exceeded those of the R and P groups (P < 0.05). Remimazolam combined with low-dose propofol effectively balances the strengths and weaknesses of remimazolam and propofol, ensuring more stable hemodynamics, a lower incidence of adverse reactions, and optimal surgical conditions in pediatric fiberoptic bronchoscopy.


Subject(s)
Bronchoscopy , Propofol , Humans , Bronchoscopy/methods , Propofol/administration & dosage , Female , Male , Child, Preschool , Child , Blood Pressure/drug effects , Heart Rate/drug effects , Fiber Optic Technology/methods , Infant , Hypnotics and Sedatives/administration & dosage , Benzodiazepines
16.
Cardiovasc Toxicol ; 24(6): 576-586, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38691302

ABSTRACT

Hypertension is a pathological state of the metabolic syndrome that increases the risk of cardiovascular disease. Managing hypertension is challenging, and we aimed to identify the pathogenic factors and discern therapeutic targets for metabolic hypertension (MHR). An MHR rat model was established with the combined treatment of a high-sugar, high-fat diet and ethanol. Histopathological observations were performed using hematoxylin-eosin and Sirius Red staining. Transcriptome sequencing was performed to screen differentially expressed genes. The role of ubiquitin-specific protease 18 (USP18) in the proliferation, apoptosis, and oxidative stress of HUVECs was explored using Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays. Moreover, USP18 downstream signaling pathways in MHR were screened, and the effects of USP18 on these signaling pathways were investigated by western blotting. In the MHR model, total cholesterol and low-density lipoprotein levels increased, while high-density lipoprotein levels decreased. Moreover, high vessel thickness and percentage of collagen were noted along with increased malondialdehyde, decreased superoxide dismutase and catalase levels. The staining results showed that the MHR model exhibited an irregular aortic intima and disordered smooth muscle cells. There were 78 differentially expressed genes in the MHR model, and seven hub genes, including USP18, were identified. USP18 overexpression facilitated proliferation and reduced apoptosis and oxidative stress in HUVECs treated with Ang in vitro. In addition, the JAK/STAT pathway was identified as a USP18 downstream signaling pathway, and USP18 overexpression inhibited the expression of JAK/STAT pathway-related proteins. Conclusively, USP18 restrained MHR progression by promoting cell proliferation, reversing apoptosis and oxidative stress, and suppressing the JAK/STAT pathway.


Subject(s)
Apoptosis , Cell Proliferation , Disease Models, Animal , Human Umbilical Vein Endothelial Cells , Hypertension , Janus Kinases , Metabolic Syndrome , Oxidative Stress , Signal Transduction , Ubiquitin Thiolesterase , Animals , Humans , Male , Rats , Apoptosis/drug effects , Blood Pressure/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Disease Progression , Gene Expression Regulation , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/enzymology , Hypertension/metabolism , Hypertension/physiopathology , Hypertension/pathology , Hypertension/enzymology , Janus Kinases/metabolism , Metabolic Syndrome/metabolism , Metabolic Syndrome/pathology , Metabolic Syndrome/enzymology , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/enzymology , Oxidative Stress/drug effects , Rats, Sprague-Dawley , STAT Transcription Factors/metabolism , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Vascular Remodeling/drug effects
18.
Nitric Oxide ; 148: 23-33, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38697467

ABSTRACT

Dietary nitrate (NO3-) supplementation can increase nitric oxide (NO) bioavailability, reduce blood pressure (BP) and improve muscle contractile function in humans. Plasma nitrite concentration (plasma [NO2-]) is the most oft-used biomarker of NO bioavailability. However, it is unclear which of several NO biomarkers (NO3-, NO2-, S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle correlate with the physiological effects of acute and chronic dietary NO3- supplementation. Using a randomized, double-blind, crossover design, 12 participants (9 males) consumed NO3--rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3--depleted placebo beetroot juice (PL) acutely and then chronically (for two weeks). Biological samples were collected, resting BP was assessed, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5-3.5 h following supplement ingestion on day 1 and day 14. Diastolic BP was significantly lower in BR (-2 ± 3 mmHg, P = 0.03) compared to PL following acute supplementation, while the absolute rate of torque development (RTD) was significantly greater in BR at 0-30 ms (39 ± 57 N m s-1, P = 0.03) and 0-50 ms (79 ± 99 N m s-1, P = 0.02) compared to PL following two weeks supplementation. Greater WB [RSNOs] rather than plasma [NO2-] was correlated with lower diastolic BP (r = -0.68, P = 0.02) in BR compared to PL following acute supplementation, while greater skeletal muscle [NO3-] was correlated with greater RTD at 0-30 ms (r = 0.64, P=0.03) in BR compared to PL following chronic supplementation. We conclude that [RSNOs] in blood, and [NO3-] in skeletal muscle, are relevant biomarkers of NO bioavailability which are related to the reduction of BP and the enhanced muscle contractile function following dietary NO3- ingestion in humans.


Subject(s)
Biomarkers , Blood Pressure , Cross-Over Studies , Dietary Supplements , Nitrates , Nitric Oxide , Humans , Nitrates/administration & dosage , Nitrates/pharmacology , Nitrates/blood , Male , Biomarkers/blood , Female , Nitric Oxide/metabolism , Nitric Oxide/blood , Adult , Double-Blind Method , Blood Pressure/drug effects , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Young Adult , Beta vulgaris/chemistry , Nitrites/blood
19.
Article in English | MEDLINE | ID: mdl-38745445

ABSTRACT

BACKGROUND: Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure. METHODS: In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups. RESULTS: There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29 mm Hg (IQR 19 to 41) compared with 31.8 mm Hg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups. CONCLUSIONS: We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.


Subject(s)
Bronchoscopy , Phenylephrine , Vasoconstrictor Agents , Humans , Phenylephrine/administration & dosage , Phenylephrine/adverse effects , Retrospective Studies , Bronchoscopy/adverse effects , Bronchoscopy/methods , Male , Female , Middle Aged , Aged , Vasoconstrictor Agents/administration & dosage , Vasoconstrictor Agents/adverse effects , Hypertension/drug therapy , Blood Pressure/drug effects
20.
Food Funct ; 15(10): 5527-5538, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38700280

ABSTRACT

The salty oligopeptides from Stropharia rugosoannulata have been proven to be potential ACE inhibitors. To investigate the ACE receptor binding properties and interaction mechanisms of salty oligopeptides, the molecular interaction, dynamics simulation, and antihypertensive evaluation cross-validation strategy were employed to reveal the oligopeptides' binding reactions and modes with the ACE receptor. Single oligopeptide (ESPERPFL, KSWDDFFTR) had exothermic and specific binding reactions with the ACE receptor, driven by hydrogen bonds and van der Waals forces. The coexistence of the multiple oligopeptide molecules did not produce the apparent ACE receptor competition binding reactions. The molecular dynamics simulation verified that the two oligopeptides disturbed the ACE receptor's different residue regions. Both oligopeptides could form stable complexes with the ACE receptor. Based on the classification of 50 oligopeptides' binding modes, ESPERPFL and KSWDDFFTR belonged to different classes, and their receptor binding modes and sites complemented, resulting in a potential synergistic effect on ACE inhibition. The antihypertensive effect of KSWDDFFTR and its distribution in the body were evaluated using SHR rats orally and ICR mice by tail vein injection, and KSWDDFFTR had antihypertensive effects within 8 h. The study provides a theoretical basis for understanding salty oligopeptides' ACE receptor binding mechanism and their antihypertensive effects.


Subject(s)
Antihypertensive Agents , Molecular Dynamics Simulation , Oligopeptides , Animals , Oligopeptides/pharmacology , Oligopeptides/chemistry , Oligopeptides/metabolism , Antihypertensive Agents/pharmacology , Antihypertensive Agents/chemistry , Rats , Male , Peptidyl-Dipeptidase A/metabolism , Peptidyl-Dipeptidase A/chemistry , Agaricales/chemistry , Agaricales/metabolism , Mice , Hypertension/drug therapy , Hypertension/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/metabolism , Protein Binding , Blood Pressure/drug effects , Rats, Inbred SHR
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