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PloS One 2013β-blockers (BBs) with different pharmacological properties may have heterogeneous effects on sympathetic nervous activity (SNA) and central aortic pressure (CAP), which... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized controlled study on the effects of bisoprolol and atenolol on sympathetic nervous activity and central aortic pressure in patients with essential hypertension.
OBJECTIVE
β-blockers (BBs) with different pharmacological properties may have heterogeneous effects on sympathetic nervous activity (SNA) and central aortic pressure (CAP), which are independent cardiovascular factors for hypertension. Hence, we analyzed the effects of bisoprolol and atenolol on SNA and CAP in hypertensive patients.
METHODS
This was a prospective, randomized, controlled study in 109 never-treated hypertensive subjects randomized to bisoprolol (5 mg) or atenolol (50 mg) for 4-8 weeks. SNA, baroreflex sensitivity (BRS) and heart rate (HR) variability (HRV) were measured using power spectral analysis using a Finometer. CAP and related parameters were determined using the SphygmoCor device (pulse wave analysis).
RESULTS
Both drugs were similarly effective in reducing brachial BP. However, central systolic BP (-14±10 mm Hg vs -6±9 mm Hg; P<0.001) and aortic pulse pressure (-3±10 mm Hg vs +3±8 mm Hg; P<0.001) decreased more significantly with bisoprolol than with atenolol. The augmentation index at a HR of 75 bpm (AIxatHR75) was significantly decreased (29%±11% to 25%±12%; P = 0.026) in the bisoprolol group only. Furthermore, the change in BRS in the bisoprolol group (3.99±4.19 ms/mmHg) was higher than in the atenolol group (2.66±3.78 ms/mmHg), although not statistically significant (P>0.05). BRS was stable when RHR was controlled (RHR≤65 bpm), and the two treatments had similar effects on the low frequency/high frequency (HF) ratio and on HF.
CONCLUSION
BBs seem to have different effects on arterial distensibility and compliance in hypertensive subjects. Compared with atenolol, bisoprolol may have a better effect on CAP.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01762436.
Topics: Adult; Antihypertensive Agents; Arterial Pressure; Atenolol; Baroreflex; Bisoprolol; Essential Hypertension; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Prospective Studies; Treatment Outcome
PubMed: 24039738
DOI: 10.1371/journal.pone.0072102 -
Cells Oct 2022Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture...
Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood-brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier.
Topics: Humans; Atenolol; Blood-Brain Barrier; Brain; Induced Pluripotent Stem Cells; Liver; Pharmaceutical Preparations; Propranolol
PubMed: 36291161
DOI: 10.3390/cells11203295 -
Journal of Cellular and Molecular... Apr 2009Combinations therapy is often used in hypertensive patients whether combination therapy is necessary for preventing end-organ damage is not known. The objective of this...
Combinations therapy is often used in hypertensive patients whether combination therapy is necessary for preventing end-organ damage is not known. The objective of this study was to determine in four different hypertensive animal models the necessity of adding the calcium channel blocker amlodipine to therapy with the ss-blocker atenolol to modulate end-organ damage. Spontaneously hypertensive rats, DOCA-salt hypertensive rats, two-kidney, one-clip renovascular hypertensive rats and Lyon genetically hypertensive rats were used to study this objective. These animal models have different sensitivities to atenolol and amlodipine. The dosages of therapy employed were 10 mg/kg atenolol alone, 1 mg/kg amlodipine, 10 mg atenolol + 1 mg/kg amlodipine and 5 mg/kg atenolol+0.5 mg/kg amlodipine. BP was continuously recorded in all animals. After determination of baroreflex sensitivity, rats were sacrificed for end-organ damage evaluation. The combination of amlodipine and atenolol had a synergistic inhibitory effect on blood pressure and blood pressure variability, and end-organ damage as compared with monotherapy with atenolol or amlodipine in all animal models. Baroreflex sensitivity also improved with the combination therapy more than with monotherapy. In conclusion, atenolol and amlodipine combination exerts a superior effect on blood pressure, blood pressure variability, baroreflex sensitivity and end-organ damage. The superior effect of the combination was observed in all four models of hypertension.
Topics: Amlodipine; Animals; Atenolol; Blood Pressure; Drug Therapy, Combination; Hemodynamics; Hypertension; Male; Organ Specificity; Rats; Rats, Sprague-Dawley; Regression Analysis; Time Factors
PubMed: 19220584
DOI: 10.1111/j.1582-4934.2008.00365.x -
British Journal of Clinical Pharmacology Jul 19881. Fourteen patients (mean age 56.0, range 37-61 years; eight females) with mild essential hypertension (DBP greater than 90 mm Hg on placebo) completed a randomised,... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1. Fourteen patients (mean age 56.0, range 37-61 years; eight females) with mild essential hypertension (DBP greater than 90 mm Hg on placebo) completed a randomised, double-blind placebo controlled crossover study comparing the hypotensive effects of bisoprolol (10-20 mg) and atenolol (50-100 mg) each taken once daily. 2. Bisoprolol had a significantly greater antihypertensive effect than atenolol, reducing sitting blood pressures by 15.9 mm Hg (diastolic) and 21.9 mm Hg (systolic) compared with placebo. Corresponding figures for atenolol were 10.7 and 5.7 mm Hg respectively. Bisoprolol reduced standing blood pressures by 15.9 mm Hg (diastolic) and 22.8 mm Hg (systolic) compared with 7.3 and 8.6 mm Hg respectively for atenolol. 3. Examination of the pharmacokinetic data showed that bisoprolol had a median elimination half-life of 11.2 h during chronic dosing, compared with 6.4 h for atenolol. For bisoprolol, the median clearance fell from 264 ml min-1 after a single dose to 212 ml min-1 during chronic dosing, although clinically significant accumulation would not be expected during chronic administration. 4. Overall, the results suggest that bisoprolol may be a more effective antihypertensive agent than atenolol but larger studies are necessary to confirm these findings.
Topics: Adrenergic beta-Antagonists; Adult; Atenolol; Bisoprolol; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Propanolamines; Random Allocation; Time Factors
PubMed: 2904825
DOI: 10.1111/j.1365-2125.1988.tb03363.x -
British Journal of Clinical Pharmacology 1984The influence of chronic therapy with nifedipine on the pharmacokinetics of propranolol 80 mg twice daily, metoprolol 100 mg twice daily and atenolol 100 mg once daily...
The influence of chronic therapy with nifedipine on the pharmacokinetics of propranolol 80 mg twice daily, metoprolol 100 mg twice daily and atenolol 100 mg once daily was investigated in eight healthy volunteers. Nifedipine 10 mg three times daily did not affect the pharmacokinetics of metoprolol and atenolol whereas nifedipine shortened the time to peak plasma concentration for propranolol by about 1 h. Propranolol, metoprolol and atenolol provoked comparable decreases in heart rate measured at rest and during exercise. The beta-adrenoceptor blocking properties of propranolol, metoprolol and atenolol were not affected by concomitant therapy with nifedipine. The present study did not show significant pharmacokinetic and pharmacodynamic interactions between nifedipine and lipophilic beta-adrenoceptor blockers.
Topics: Adrenergic beta-Antagonists; Adult; Atenolol; Drug Interactions; Humans; Kinetics; Male; Metoprolol; Nifedipine; Propranolol
PubMed: 6146337
DOI: 10.1111/j.1365-2125.1984.tb02425.x -
Acta Cirurgica Brasileira Nov 2017To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model.
PURPOSE
To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model.
METHODS
Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA.
RESULTS
The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats.
CONCLUSION
Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.
Topics: Animals; Antihypertensive Agents; Atenolol; Cardiovascular Diseases; Heart; Intestines; Male; Mesenteric Artery, Superior; Rats; Rats, Wistar; Reperfusion Injury
PubMed: 29236801
DOI: 10.1590/s0102-865020170110000008 -
BMJ (Clinical Research Ed.) Mar 1993
Topics: Atenolol; England; Female; Humans; Hypertension; Male; Middle Aged; Neoplasms; Risk Factors
PubMed: 8461813
DOI: 10.1136/bmj.306.6878.622 -
British Journal of Clinical Pharmacology Jul 1981Bronchial and cardiac beta-adrenoceptor blockade have been compared in six normal subjects after three beta-adrenoceptor antagonists. Single and double doses of atenolol... (Comparative Study)
Comparative Study
Bronchial and cardiac beta-adrenoceptor blockade have been compared in six normal subjects after three beta-adrenoceptor antagonists. Single and double doses of atenolol (50 and 100 mg), acebutolol (100 and 200 mg) and labetalolol (150 and 300 mg) were studied on separate occasions. 2 Salbutamol airway dose-response curves were obtained by measuring the airway response as the change in specific airway conductance (sGaw) after increasing doses of inhaled salbutamol. Bronchial beta-adrenoceptor blockade was assessed after each drug as the dose of salbutamol needed to cause a 50% increase in sGaw (sGaw D50). 3 Cardiac beta-adrenoceptor blockade was assessed after the same doses of each beta-adrenoceptor antagonist, by measuring the percentage reduction in exercise heart rate from control, after exercise for 5 min at 70% of the subject's maximum work rate. 4 Atenolol 50 and 100 mg caused least bronchial beta-adrenoceptor blockade and the greatest reduction in exercise heart rate. 5 Acebutolol 100 and 200 mg and labetalol 150 and 300 mg produced more bronchial beta-adrenoceptor blockade than atenolol. 6 With this approach new beta-adrenoceptor antagonists can be assessed without putting asthmatic patients at risk.
Topics: Acebutolol; Airway Resistance; Atenolol; Bronchi; Dose-Response Relationship, Drug; Ethanolamines; Heart; Heart Rate; Humans; Labetalol; Physical Exertion; Propanolamines; Receptors, Adrenergic; Receptors, Adrenergic, beta
PubMed: 6264936
DOI: 10.1111/j.1365-2125.1981.tb01855.x -
American Journal of Veterinary Research Oct 2021To investigate associations between short-term treatment with a previously described compounded transdermal formulation of atenolol and heart rate in cats.
OBJECTIVE
To investigate associations between short-term treatment with a previously described compounded transdermal formulation of atenolol and heart rate in cats.
ANIMALS
11 healthy adult cats.
PROCEDURES
Cats received the atenolol gel formulation (gradually increased from 12.5 mg/cat, q 24 h to 25 mg/cat, q 12 h) by application to the pinnae at home over a 10-day period in a prospective, experimental study. On day 10, cats were hospitalized for measurement of serum atenolol concentrations 3, 6, and 12 hours after the morning treatment. Mean heart rate measured at the 3- and 6-hour time points was compared with a baseline value (measured at enrollment).
RESULTS
All cats completed the study; 4 were excluded from analyses after an apparent formulation error was detected in 1 batch. Two cats had minor adverse effects (localized erythema of the pinna). Five of 7 cats had serum atenolol concentrations ≥ 260 ng/mL (considered therapeutic) at ≥ 1 time point. Heart rate had a strong negative correlation ( = -0.87) with serum atenolol concentration. A 90-day drug stability investigation of 4 formulations (identical to the intended study treatment except for pH [range, 6.5 to 7.7]) revealed an apparent decrease in atenolol concentration at a pH of 7.7.
CONCLUSIONS AND CLINICAL RELEVANCE
Topical administration of the formulation as described resulted in targeted serum atenolol concentrations in most cats, with attendant HR reduction. Validation of these preliminary results in a larger sample and investigation of the treatment in cats with structural heart disease is needed. Verification of appropriate pH (target, 7.0) is likely essential for the compound's stability.
Topics: Administration, Cutaneous; Animals; Atenolol; Heart Rate; Prospective Studies
PubMed: 34554869
DOI: 10.2460/ajvr.82.10.811 -
Pharmacotherapy Sep 2010To evaluate whether the level of systemic exposure to atenolol explains observed interindividual differences in adverse metabolic responses. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
To evaluate whether the level of systemic exposure to atenolol explains observed interindividual differences in adverse metabolic responses.
DESIGN
Open-label, prospective, pharmacokinetic pilot substudy of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study.
SETTING
General clinical research center.
PATIENTS
Fifteen hypertensive adults (mean age 46 +/- 8.9 yrs) who were enrolled in the PEAR study.
INTERVENTION
Patients received atenolol therapy for at least 8 weeks, with 5 of those weeks at a dosage of 100 mg/day, and then underwent a 2-hour oral glucose tolerance test during a pharmacokinetic study visit.
MEASUREMENTS AND MAIN RESULTS
Twenty-hour plasma atenolol concentrations were measured during the pharmacokinetic visit. Glucose and insulin levels were measured during the 2-hour oral glucose tolerance test, and fasting plasma lipid, glucose, and insulin levels were measured at baseline and after 8 weeks of atenolol treatment. A significant association was noted between atenolol area under the concentration-time curve (AUC) and change in fasting glucose level when adjusted for covariates (p=0.0025); the effect was strongest in women. No significant relationship was noted between plasma atenolol concentration and glucose AUC during oral glucose tolerance testing (r=0.08, p=0.78), nor between atenolol AUC and change in triglyceride levels (r=0.13, p=0.63).
CONCLUSION
Higher plasma atenolol exposure may be a risk factor for an increase in fasting plasma glucose level during atenolol treatment. These findings require confirmation in a larger sample.
Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Atenolol; Blood Glucose; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Lipids; Male; Middle Aged; Pilot Projects; Risk Factors; Young Adult
PubMed: 20795842
DOI: 10.1592/phco.30.9.872