Effects of E-Adrenoceptor Antagonists on Exercise-Induced Cardiovascular Changes
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AI Summary
This experimental study sought to assess the effects of orally administered E-adrenoceptor antagonists, atenolol and pindolol, on blood pressure, heart rate and lung function at rest and after exercise. The study used university students as subjects and the results signified that, the drugs had an effect on blood pressure, heart rate and lung functionality at rest state. The beta blockers lowered the blood pressure, reduced heart rate and improved lung function. There were reduced levels of fatigue level on post drug administration. There was not significant effect on exercise both at rest and during exercise.
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RUNNING HEAD ; LAB REPORT
THE EFFECTS OF E-ADRENOCEPTOR ANTAGONISTS ON EXERCISE
INDUCED CARDIOVASCULAR CHANGES
Name
University
ASSIGNMENT
THE EFFECTS OF E-ADRENOCEPTOR ANTAGONISTS ON EXERCISE
INDUCED CARDIOVASCULAR CHANGES
Name
University
ASSIGNMENT
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LAB REPORT
Abstract
Beta blockers commonly E-adrenoceptor antagonists have been used to lower blood
levels. Beta blockers are used in aerobic performances and this aspect has been used
in treatment effects of cardiovascular disease. The effect of beta blockers are to block
the binding effect of norepinephrine and epinephrine, the sympathetic effect of the
beta blockers have been found to have an effect in lowering the level of
cardiovascular. This experimental study sought to assess the effects of orally
administered E-adrenoceptor antagonists, atenolol and pindolol, on blood pressure,
heart rate and lung function at rest and after exercise. The study used university
students as subjects and the results signified that, the drugs had an effect on blood
pressure, heart rate and lung functionality at rest state. The beta blockers lowered the
blood pressure, reduced heart rate and improved lung function. There were reduced
levels of fatigue level on post drug administration. There was not significant effect on
exercise both at rest and during exercise
.
Abstract
Beta blockers commonly E-adrenoceptor antagonists have been used to lower blood
levels. Beta blockers are used in aerobic performances and this aspect has been used
in treatment effects of cardiovascular disease. The effect of beta blockers are to block
the binding effect of norepinephrine and epinephrine, the sympathetic effect of the
beta blockers have been found to have an effect in lowering the level of
cardiovascular. This experimental study sought to assess the effects of orally
administered E-adrenoceptor antagonists, atenolol and pindolol, on blood pressure,
heart rate and lung function at rest and after exercise. The study used university
students as subjects and the results signified that, the drugs had an effect on blood
pressure, heart rate and lung functionality at rest state. The beta blockers lowered the
blood pressure, reduced heart rate and improved lung function. There were reduced
levels of fatigue level on post drug administration. There was not significant effect on
exercise both at rest and during exercise
.
LAB REPORT
Introduction
Beta – adrenoceptors are binded by beta blockers drugs which block the binding of
norepinephrine and epinephrine receptors. These cause inhibition of the effects which act on
the receptors. Beta blockers act as drugs which are sympatholytic. Often beta blockers bind to
beta-adrenoceptors which partially activates the receptors which activates them while
offering prevention of norepinephrine from binding the receptor. The partial agonists thus
provide backgrounds for sympathetic activity while offering prevention of normal and
enhanced sympathetic activity. The beta blockers possess aspect of intrinsic
sympathomimetic activity while others produce stabilizing activity, thus producing similar
activites as observed on membrane stabilization activity by sodium channels blockers.i
Beta blockers bind themselves to beta adrenoceptors which are located in cardiac area
surrounding the nodal tissue, which conduct the system and offers contraction of myocytes.
The beat has been shown to have both β1 and β2 adrenoceptors, which the common is β1
adrenoceptors. It offers binding effect on the norepinephrine which releases itself to
sympathetic nerves located in adrenergic area. Beta blockers in this case offer binding
protection to normal ligand β-adrenoceptors through competing itself on the binding sites.ii
Beta adrenoceptors are coupled by the Gs protein which offers activation of adenyl
cyclase forming Camp located in the ATP which increases the Camp and thus activated the
dependent protein kinase. With the general level of sympathetic tone in the heart, these beta
blockers are able to lower down the sympathetic influence which offers stimulation of the
heart rate, contractility, electrical conduction and relaxation. This leads to reduction in heart
rate, contractility, velocity conduction and relaxation. These kinds of drugs have been shown
to have an effect on the elevated levels of sympathetic activity.iii
With concern of cardiovascular health, beta blockers often offer little vascular effect
due to the β2 adrenoceptors having small function of the modulator in the basal vascular tone.
Blockage of β2 adrenoceptors is linked to smaller degree of vasoconstriction in the vascular
beds.iv
Studies have shown that β1 and β2 adrenoceptor receptors are associated increased
intensity of vascular activity, it stimulates in response to the constriction and relaxation of the
arteries and veins.v Endothelial cells are not produced through mediation of β1 and β2
adrenoceptors, rather they play a key role in influcneing blood vessel activity, further the role
played the vascular activity is key in prevention and treatment of vascular disease, thus
assessing the different morphology of cardiac function is relevant in establishing effects of β1
and β2 adrenoceptors. vi
Introduction
Beta – adrenoceptors are binded by beta blockers drugs which block the binding of
norepinephrine and epinephrine receptors. These cause inhibition of the effects which act on
the receptors. Beta blockers act as drugs which are sympatholytic. Often beta blockers bind to
beta-adrenoceptors which partially activates the receptors which activates them while
offering prevention of norepinephrine from binding the receptor. The partial agonists thus
provide backgrounds for sympathetic activity while offering prevention of normal and
enhanced sympathetic activity. The beta blockers possess aspect of intrinsic
sympathomimetic activity while others produce stabilizing activity, thus producing similar
activites as observed on membrane stabilization activity by sodium channels blockers.i
Beta blockers bind themselves to beta adrenoceptors which are located in cardiac area
surrounding the nodal tissue, which conduct the system and offers contraction of myocytes.
The beat has been shown to have both β1 and β2 adrenoceptors, which the common is β1
adrenoceptors. It offers binding effect on the norepinephrine which releases itself to
sympathetic nerves located in adrenergic area. Beta blockers in this case offer binding
protection to normal ligand β-adrenoceptors through competing itself on the binding sites.ii
Beta adrenoceptors are coupled by the Gs protein which offers activation of adenyl
cyclase forming Camp located in the ATP which increases the Camp and thus activated the
dependent protein kinase. With the general level of sympathetic tone in the heart, these beta
blockers are able to lower down the sympathetic influence which offers stimulation of the
heart rate, contractility, electrical conduction and relaxation. This leads to reduction in heart
rate, contractility, velocity conduction and relaxation. These kinds of drugs have been shown
to have an effect on the elevated levels of sympathetic activity.iii
With concern of cardiovascular health, beta blockers often offer little vascular effect
due to the β2 adrenoceptors having small function of the modulator in the basal vascular tone.
Blockage of β2 adrenoceptors is linked to smaller degree of vasoconstriction in the vascular
beds.iv
Studies have shown that β1 and β2 adrenoceptor receptors are associated increased
intensity of vascular activity, it stimulates in response to the constriction and relaxation of the
arteries and veins.v Endothelial cells are not produced through mediation of β1 and β2
adrenoceptors, rather they play a key role in influcneing blood vessel activity, further the role
played the vascular activity is key in prevention and treatment of vascular disease, thus
assessing the different morphology of cardiac function is relevant in establishing effects of β1
and β2 adrenoceptors. vi
LAB REPORT
Beta-adrenoceptor antagonists function in cardiovascular management by lowering
elevated blood pressure. Compounds such as Atenol selectively apply to Beta 1-adrenoceptor
which possess intrinsic sympathomimetic activity. vii Pindol on the other hand has non
selective ability of beta-adrenoceptor which possesses sympathomimetic activity. These study
evaluates its application when used in two body states that is during rest and exercise
activities, medical and therapeutic effects of both drugs is being tested. The study is a double
blind using vitamin B6 as a placebo control.
This study thus seeks to examine the effects of orally administered β adrenoceptors
antagonists, Atenolol and Pendolol on the blood pressure effects, heart rate and lung function
during two critical phases of rest and after exercise activity.
Methods and materials
The study experiment was submitted to the University of New South Wales, health
science department for ethical approval. This experimental study employed double blind
design , where subjects were blinded and utilized placebo and control usage. The subject
participants involved students aged between 18-65 years of the University of New South
Wales.
The materials need for this study included Perceived Exertion Scale, heart rate monitor
having watch, strap and polar, blood pressure monitor, peak flow meter and a timer. The
experimental phase involved two stages; pre drug and post drug . at the pre drug phase, the
start the timer at 0 minutes and time adjusted to resistance level to obtain the KP level, then
hold KP level at 50rpm for 2 minutes. During the last 10 seconds, recording of the heart rate,
(EHR) and exertion level are undertaken. At 15 minutes recoding s of resting heart rate
(RHR) is taken, while at 30 minutes, RHR, oxygen saturation, blood pressure and lung
function is undertaken. Then bike exercise undertaken while the KP levels is set at 2 minutes
repeat the assessment of EHR, oxygen saturation and exertion levels.
At post drug level, drug is consumed and measurements taken at 15 minutes rest, record
thee RHR, oxygen saturation, blood pressure and lung function test for the participant, again
the assessments are undertaken at 30 minutes , rest, 45 minutes rest, 60 minutes rest, 75
minutes rest and 90 minutes rest post drug ingestion rest level . after 90 minutes start the
bike then set at KP levels for 2 minutes then take the assessments of HER, oxygen saturation
and exertion level.
Beta-adrenoceptor antagonists function in cardiovascular management by lowering
elevated blood pressure. Compounds such as Atenol selectively apply to Beta 1-adrenoceptor
which possess intrinsic sympathomimetic activity. vii Pindol on the other hand has non
selective ability of beta-adrenoceptor which possesses sympathomimetic activity. These study
evaluates its application when used in two body states that is during rest and exercise
activities, medical and therapeutic effects of both drugs is being tested. The study is a double
blind using vitamin B6 as a placebo control.
This study thus seeks to examine the effects of orally administered β adrenoceptors
antagonists, Atenolol and Pendolol on the blood pressure effects, heart rate and lung function
during two critical phases of rest and after exercise activity.
Methods and materials
The study experiment was submitted to the University of New South Wales, health
science department for ethical approval. This experimental study employed double blind
design , where subjects were blinded and utilized placebo and control usage. The subject
participants involved students aged between 18-65 years of the University of New South
Wales.
The materials need for this study included Perceived Exertion Scale, heart rate monitor
having watch, strap and polar, blood pressure monitor, peak flow meter and a timer. The
experimental phase involved two stages; pre drug and post drug . at the pre drug phase, the
start the timer at 0 minutes and time adjusted to resistance level to obtain the KP level, then
hold KP level at 50rpm for 2 minutes. During the last 10 seconds, recording of the heart rate,
(EHR) and exertion level are undertaken. At 15 minutes recoding s of resting heart rate
(RHR) is taken, while at 30 minutes, RHR, oxygen saturation, blood pressure and lung
function is undertaken. Then bike exercise undertaken while the KP levels is set at 2 minutes
repeat the assessment of EHR, oxygen saturation and exertion levels.
At post drug level, drug is consumed and measurements taken at 15 minutes rest, record
thee RHR, oxygen saturation, blood pressure and lung function test for the participant, again
the assessments are undertaken at 30 minutes , rest, 45 minutes rest, 60 minutes rest, 75
minutes rest and 90 minutes rest post drug ingestion rest level . after 90 minutes start the
bike then set at KP levels for 2 minutes then take the assessments of HER, oxygen saturation
and exertion level.
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LAB REPORT
Results
Pre drug treatment results
Time/
min
Resting
heart rate
beats/min
BP-
dbp/sbp
mmHg
PEFR
L/min
ROS
SpO2
%
EOS EHR
Beats/
min
Fatigue
Rest Exercise
0 82 115/76 434 98 97 399 10.6
15 87 116/75 441 97
30 86 113/74 445 97 95 114 11
Average 84 117/75 440 97 97 215 11.2
Table 1 showing the pre drug assessment of the various assessment indicators.
Key ; PEFR(Peak expiratory flow rate), ROS( rate of oxygen saturation ),
EOS(Exercise oxygen saturation), HER- (Heart exercise rate)
Post drug treatment results
Table 2 showing the blood pressure assessment
Table 2 : showing resting heart rate
Time/min PEFRL/min
Vit B6 Atenolol Pendalol
60 475 451 415
90 460 456 450
120 480 457 451
Average 471 451 438
Table 3 showing the rate of peak expiratory rate
Time/min ROS
SpO2%
Time/min SBP/DBP mmHg
Vit B6 Atenolol Pendalol
60 117/72 113/69 106/70
90 118/70 107/67 104/65
120 115/69 108/70 101/64
Average 116/71 109/68 103/66
Time/min RHR beats/min
Vit B6 Atenolol Pendalol
60 79 79.5 71
90 79 79 72
120 82 82 71
Average 80 80 71.5
Results
Pre drug treatment results
Time/
min
Resting
heart rate
beats/min
BP-
dbp/sbp
mmHg
PEFR
L/min
ROS
SpO2
%
EOS EHR
Beats/
min
Fatigue
Rest Exercise
0 82 115/76 434 98 97 399 10.6
15 87 116/75 441 97
30 86 113/74 445 97 95 114 11
Average 84 117/75 440 97 97 215 11.2
Table 1 showing the pre drug assessment of the various assessment indicators.
Key ; PEFR(Peak expiratory flow rate), ROS( rate of oxygen saturation ),
EOS(Exercise oxygen saturation), HER- (Heart exercise rate)
Post drug treatment results
Table 2 showing the blood pressure assessment
Table 2 : showing resting heart rate
Time/min PEFRL/min
Vit B6 Atenolol Pendalol
60 475 451 415
90 460 456 450
120 480 457 451
Average 471 451 438
Table 3 showing the rate of peak expiratory rate
Time/min ROS
SpO2%
Time/min SBP/DBP mmHg
Vit B6 Atenolol Pendalol
60 117/72 113/69 106/70
90 118/70 107/67 104/65
120 115/69 108/70 101/64
Average 116/71 109/68 103/66
Time/min RHR beats/min
Vit B6 Atenolol Pendalol
60 79 79.5 71
90 79 79 72
120 82 82 71
Average 80 80 71.5
LAB REPORT
Vit B6 Atenolol Pendalol
60 97.6 98 97.08
90 97.3 98.16 97.03
120 97.5 97.3 97
Average 97.4 97.6 97
Table 4 showing rate of oxygen saturation
Results after exercise
Resting heart rate
Time Resting heart rate
beats/min
Vit B6 Atenolol Pendalol
60 123 116 103
90 130 112 96.8
120 130 102 98.8
Average 127 110 99
Table 5 showing resting heart rate
Exercise oxygen saturation levels
Time/min EOS
Vit B6 Atenolol Pendalol
60 97.6 97.33 96.5
90 98 97.5 97
120 97.3 96.8 96
Average 97.5 97 96.5
Table 6 showing exercise saturation levels
Exercise fatigue levels of the assessments
Time/min Fatigue
Exertion level
Vit B6 Atenolol Pendalol
60 10.1 12.25 11.5
90 10.9 12.5 11.8
120 11.3 13 12.9
Average 10.7 12.3 11.5
Table 7 showing exercise fatigue levels
Vit B6 Atenolol Pendalol
60 97.6 98 97.08
90 97.3 98.16 97.03
120 97.5 97.3 97
Average 97.4 97.6 97
Table 4 showing rate of oxygen saturation
Results after exercise
Resting heart rate
Time Resting heart rate
beats/min
Vit B6 Atenolol Pendalol
60 123 116 103
90 130 112 96.8
120 130 102 98.8
Average 127 110 99
Table 5 showing resting heart rate
Exercise oxygen saturation levels
Time/min EOS
Vit B6 Atenolol Pendalol
60 97.6 97.33 96.5
90 98 97.5 97
120 97.3 96.8 96
Average 97.5 97 96.5
Table 6 showing exercise saturation levels
Exercise fatigue levels of the assessments
Time/min Fatigue
Exertion level
Vit B6 Atenolol Pendalol
60 10.1 12.25 11.5
90 10.9 12.5 11.8
120 11.3 13 12.9
Average 10.7 12.3 11.5
Table 7 showing exercise fatigue levels
LAB REPORT
Discussion
The results indicate that there is elevated blood pressure with intake of the treatment.
Pre drug assessments shows an average of 117/75, while on drug administration, the blood
pressure was lowered significantly to 109/68 for Atenol drug and Pendalol at 103/66 beta
blockers. Blood pressure ranges 90/60 or less, signifies low blood pressure, while between
ranges of 90/60 to 120/80 shows ideal pressure and 140/90 and above signifies high blood
pressure. The peak expiratory flow rate indicated an average of 451 L/min for Atenolol and
438 for Pednalol. The results were comparable at the pre drug phase where there was an
average of 44L/min signifying higher effect of beta blockers on lung functionality. The heart
beat rate showed an average of 215 beats/min on pre drug treatment compared to 127
beats/min for the placebo, 110 beats for Atenolol drug and 99 beats/minute for pendadol
drug. There was higher effect of the beta blockers on drug administration by lowering the
heart beats of the sample participants.
Β-Blockers being the common drugs for lowering blood pressure has been used in
hypertension management. The results in this study have showed the effect of the β-Blockers
on the blood pressure. There is lowered blood pressure both systolic and diastolic signifying
change effect. Its pharmacological effect acts on the intrinsic sympathomimetic activity
which has adrenergic properties which block production of nitrix oxide portraying
hydrophilic and lipophilic properties on blood. Combined with activity levels, it improves
health outcomes through effect of cardio respiratory effects. viii
Peak expiratory flow rate refers to the expiration speed it signifies the rate at which
there is forceful exhalation of air. It reflects airway flow and this relies heavily on the
voluntary effort and muscular ability of the patient. Maximum airflow is observed during
effort depends on expiratory maneuver. Peak expiratory rate on medication showed an
average of 97.6% under Atenol drug, 97% under pendadol drug and at 97.4% for Vitamin B
6. Compared to pre drug administration the average peak expiratory rate is 97% showing no
significant difference.
On exercise levels average resting heart rate for Atenolol and Pendadol is 110
betas/min and 99beats/min respectively compared to that of placebo which is 127 beats/min.
on pre drug assessment the heart beat rate is 215 beats/min, signifying lowered levels of heart
beat rate. Oxygen saturation rate level signifies an average of 97% on Atenolol drug, pendalol
at 96.5% compared to placebo level at 97.5%. pre drug assessment showed an average of
97% showing no signifying difference.
Fatigue levels on exercise showed an average of 12.3 levels on Atenolol drug and a
Discussion
The results indicate that there is elevated blood pressure with intake of the treatment.
Pre drug assessments shows an average of 117/75, while on drug administration, the blood
pressure was lowered significantly to 109/68 for Atenol drug and Pendalol at 103/66 beta
blockers. Blood pressure ranges 90/60 or less, signifies low blood pressure, while between
ranges of 90/60 to 120/80 shows ideal pressure and 140/90 and above signifies high blood
pressure. The peak expiratory flow rate indicated an average of 451 L/min for Atenolol and
438 for Pednalol. The results were comparable at the pre drug phase where there was an
average of 44L/min signifying higher effect of beta blockers on lung functionality. The heart
beat rate showed an average of 215 beats/min on pre drug treatment compared to 127
beats/min for the placebo, 110 beats for Atenolol drug and 99 beats/minute for pendadol
drug. There was higher effect of the beta blockers on drug administration by lowering the
heart beats of the sample participants.
Β-Blockers being the common drugs for lowering blood pressure has been used in
hypertension management. The results in this study have showed the effect of the β-Blockers
on the blood pressure. There is lowered blood pressure both systolic and diastolic signifying
change effect. Its pharmacological effect acts on the intrinsic sympathomimetic activity
which has adrenergic properties which block production of nitrix oxide portraying
hydrophilic and lipophilic properties on blood. Combined with activity levels, it improves
health outcomes through effect of cardio respiratory effects. viii
Peak expiratory flow rate refers to the expiration speed it signifies the rate at which
there is forceful exhalation of air. It reflects airway flow and this relies heavily on the
voluntary effort and muscular ability of the patient. Maximum airflow is observed during
effort depends on expiratory maneuver. Peak expiratory rate on medication showed an
average of 97.6% under Atenol drug, 97% under pendadol drug and at 97.4% for Vitamin B
6. Compared to pre drug administration the average peak expiratory rate is 97% showing no
significant difference.
On exercise levels average resting heart rate for Atenolol and Pendadol is 110
betas/min and 99beats/min respectively compared to that of placebo which is 127 beats/min.
on pre drug assessment the heart beat rate is 215 beats/min, signifying lowered levels of heart
beat rate. Oxygen saturation rate level signifies an average of 97% on Atenolol drug, pendalol
at 96.5% compared to placebo level at 97.5%. pre drug assessment showed an average of
97% showing no signifying difference.
Fatigue levels on exercise showed an average of 12.3 levels on Atenolol drug and a
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LAB REPORT
level of 11.5 on Pendalol level compared to 10.7 levels on placebo. Pre drug assessments
showed that an average of 11.2 level of fatigue showing no significant difference.
In making comparisons of different intrinsic β-blockers influence on cardiovascular
patients, has shown that the different antagonists portray similar effect on cardiovascular
activity. ix When used with exercise therapy, these results showed that it lowered significantly
the heart beat rates. Exercise has been predominalty been used in testing the effect of
treatment on cardiovascular patients. x
Thus this experiment signifies a significant effect of e-adrenoceptor antagonists on
exercise induced cardiovascular changes. Beta adrenoceptor has significant effects on the
cardiovascular health status, through lowering blood pressure, reducing the levels of heart
beat and improved levels of lung function. The different state of physical activity has no
significant difference on the effect of beta blockers in binding the receptors of nor
epinephrine and epinephrine.
References
level of 11.5 on Pendalol level compared to 10.7 levels on placebo. Pre drug assessments
showed that an average of 11.2 level of fatigue showing no significant difference.
In making comparisons of different intrinsic β-blockers influence on cardiovascular
patients, has shown that the different antagonists portray similar effect on cardiovascular
activity. ix When used with exercise therapy, these results showed that it lowered significantly
the heart beat rates. Exercise has been predominalty been used in testing the effect of
treatment on cardiovascular patients. x
Thus this experiment signifies a significant effect of e-adrenoceptor antagonists on
exercise induced cardiovascular changes. Beta adrenoceptor has significant effects on the
cardiovascular health status, through lowering blood pressure, reducing the levels of heart
beat and improved levels of lung function. The different state of physical activity has no
significant difference on the effect of beta blockers in binding the receptors of nor
epinephrine and epinephrine.
References
i Audigane, L., Kerfant, B. G., El Harchi, A., Lorenzen‐Schmidt, I., Toumaniantz, G.,
Cantereau, A., ... & Gauthier, C. (2009). Rabbit, a relevant model for the study of cardiac β3‐
adrenoceptors. Experimental physiology, 94(4), 400-411.
ii Bozkurt, B., Bolos, M., Deswal, A., Ather, S., Chan, W., Mann, D. L., & Carabello, B. (2012).
New insights into mechanisms of action of carvedilol treatment in chronic heart failure patients
—a matter of time for contractility. Journal of cardiac failure, 18(3), 183-193.
iii Ferrari, R., Anand, I. S., Ceconi, C., De Giuli, F., Poole-Wilson, P. A., & Harris, P. (1996).
Neuroendocrine response to standing and mild exercise in patients with untreated severe
congestive heart failure and chronic constrictive pericarditis. Heart, 76(1), 50-55.
iv Peller, M., Ozierański, K., Balsam, P., Grabowski, M., Filipiak, K. J., & Opolski, G. (2015).
Influence of beta-blockers on endothelial function: a meta-analysis of randomized controlled
trials. Cardiology journal, 22(6), 708-716.
v Billeh, R., Hirsh, D., Barker, C., Jorgensen, B., Jeger, R., Ramanathan, K., ... & Jorde, U. P.
(2006). Randomized, Double‐Blind Comparison of Acute β1‐Blockade With 50 mg Metoprolol
Tartrate vs 25 mg Carvedilol in Normal Subjects. Congestive Heart Failure, 12(5), 254-257.
vi Ladage, D., Schwinger, R. H., & Brixius, K. (2013). Cardio‐Selective Beta‐Blocker:
Pharmacological Evidence and Their Influence on Exercise Capacity. Cardiovascular
therapeutics, 31(2), 76-83.
vii Marazzi, G., Volterrani, M., Caminiti, G., Iaia, L., Massaro, R., Vitale, C., ... & Rosano, G.
(2011). Comparative long term effects of nebivolol and carvedilol in hypertensive heart failure
patients. Journal of cardiac failure, 17(9), 703-709.
viii Moniotte, S., & Balligand, J. L. (2002). Potential Use of β3‐Adrenoceptor Antagonists in
Heart Failure Therapy. Cardiovascular Therapeutics, 20(1), 19-26.
ix Larochelle, P., Tobe, S. W., & Lacourcière, Y. (2014). β-Blockers in hypertension: studies and
meta-analyses over the years. Canadian Journal of Cardiology, 30(5), S16-S22.
x Yun, S., Vincelette, N. D., & Abraham, I. (2015). Cardioprotective role of β-blockers and
angiotensin antagonists in early-onset anthracyclines-induced cardiotoxicity in adult patients: a
systematic review and meta-analysis. Postgraduate medical journal, 91(1081), 627-633.
Cantereau, A., ... & Gauthier, C. (2009). Rabbit, a relevant model for the study of cardiac β3‐
adrenoceptors. Experimental physiology, 94(4), 400-411.
ii Bozkurt, B., Bolos, M., Deswal, A., Ather, S., Chan, W., Mann, D. L., & Carabello, B. (2012).
New insights into mechanisms of action of carvedilol treatment in chronic heart failure patients
—a matter of time for contractility. Journal of cardiac failure, 18(3), 183-193.
iii Ferrari, R., Anand, I. S., Ceconi, C., De Giuli, F., Poole-Wilson, P. A., & Harris, P. (1996).
Neuroendocrine response to standing and mild exercise in patients with untreated severe
congestive heart failure and chronic constrictive pericarditis. Heart, 76(1), 50-55.
iv Peller, M., Ozierański, K., Balsam, P., Grabowski, M., Filipiak, K. J., & Opolski, G. (2015).
Influence of beta-blockers on endothelial function: a meta-analysis of randomized controlled
trials. Cardiology journal, 22(6), 708-716.
v Billeh, R., Hirsh, D., Barker, C., Jorgensen, B., Jeger, R., Ramanathan, K., ... & Jorde, U. P.
(2006). Randomized, Double‐Blind Comparison of Acute β1‐Blockade With 50 mg Metoprolol
Tartrate vs 25 mg Carvedilol in Normal Subjects. Congestive Heart Failure, 12(5), 254-257.
vi Ladage, D., Schwinger, R. H., & Brixius, K. (2013). Cardio‐Selective Beta‐Blocker:
Pharmacological Evidence and Their Influence on Exercise Capacity. Cardiovascular
therapeutics, 31(2), 76-83.
vii Marazzi, G., Volterrani, M., Caminiti, G., Iaia, L., Massaro, R., Vitale, C., ... & Rosano, G.
(2011). Comparative long term effects of nebivolol and carvedilol in hypertensive heart failure
patients. Journal of cardiac failure, 17(9), 703-709.
viii Moniotte, S., & Balligand, J. L. (2002). Potential Use of β3‐Adrenoceptor Antagonists in
Heart Failure Therapy. Cardiovascular Therapeutics, 20(1), 19-26.
ix Larochelle, P., Tobe, S. W., & Lacourcière, Y. (2014). β-Blockers in hypertension: studies and
meta-analyses over the years. Canadian Journal of Cardiology, 30(5), S16-S22.
x Yun, S., Vincelette, N. D., & Abraham, I. (2015). Cardioprotective role of β-blockers and
angiotensin antagonists in early-onset anthracyclines-induced cardiotoxicity in adult patients: a
systematic review and meta-analysis. Postgraduate medical journal, 91(1081), 627-633.
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