Differential effects of selective versus nonselective alpha adrenergic receptor blockade on cardiovascular (CV) parameters and heart rate variability (HRV) in rats

Abstract Background: Beta-blockers are increasingly prescribed while the effects of beta-adrenergic receptor blockade on cardio-pulmonary exercise test (CPET) derived parameters remain under-studied. Methods: 21 young healthy adults repeated 3 CPET at an interval of 7 days at the same time of the day. The tests were performed 3 hours after a random, double blind, cross-over single dose intake of placebo, 2.5 mg bisoprolol or 5 mg bisoprolol. Gaz exchange, heart rate and blood pressure were measured at rest and during cyclo-ergometric CPET.Results: Maximal workload and VO2max were unaffected by the treatment, with maximal respiratory exchange ratio > 1.15 in all tests. A beta-blocker dose-dependent effect reduced resting and maximal blood pressure and heart rate and the chronotropic response to exercise, evaluated by the heart rate/VO2 slope (placebo: 2,9 ± 0,4 beat/ml/kg; 2,5 mg bisoprolol: 2,4 ± 0,5 beat/ml/kg; 5 mg bisoprolol: 2,3 ± 0,4 beat/ml/kg, p<0.001). Ventilation efficiency measured by the VE/VCO2 slope and the ventilatory equivalent for CO2 at the ventilatory threshold were not affected by beta1-receptor blockade. Post-exercise chronotropic recovery measured after 1 min was enhanced under beta1-blocker (placebo: 26 ± 7 bpm; 2,5 mg bisoprolol: 32 ± 6 bpm; 5 mg bisoprolol: 33 ± 6 bpm, p<0.01).Conclusion: The present results suggest that a single dose of bisoprolol does not affect metabolism, respiratory response and exercise capacity. However, beta-adrenergic blockade dose-dependently reduced exercise hemodynamic response by lowering the pressure and chronotropic responses.

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Neurally mediated cardiac effects of forskolin in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.4.h1473 ◽

1996 ◽

Vol 271 (4) ◽

pp. H1473-H1482 ◽

Cited By ~ 2

Author(s):

M. Iwase ◽

Y. Ishikawa ◽

Y. T. Shen ◽

R. P. Shannon ◽

N. Sato ◽

...

Keyword(s):

Heart Rate ◽

Adenylyl Cyclase ◽

Adrenergic Receptor ◽

Left Ventricular ◽

Conscious Dogs ◽

Receptor Blockade ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Ganglionic Blockade ◽

Adrenergic Receptor Blockade

Because major cardiovascular disease states are characterized by defects in adenylyl cyclase regulation, it becomes important to understand the mechanisms by which adenylyl cyclase activators affect inotropy and chronotropy in intact conscious animals. Accordingly, we examined the inotropic and chronotropic responses to forskolin in 11 normal conscious, chronically instrumented dogs and 3 dogs with ventricular denervation (VD). Left ventricular first derivative of pressure (LV dP/dt) increased by 96 +/- 7%, P < 0.05, in response to forskolin (50 nmol.kg-1.min-1) in normal dogs and by significantly less, 52 +/- 14%, in VD dogs. Circulating norepinephrine (NE) levels increased similarly in both groups (from 226 +/- 18 to 389 +/- 33 pg/ml in normal dogs, from 177 +/- 23 to 329 +/- 71 pg/ml in VD dogs). In the presence of ganglionic blockade, the increase in LV dP/dt in response to forskolin was reduced (+62 +/- 4%) in normal dogs but was unchanged in VD dogs (+52 +/- 12%). Ganglionic blockade abolished the increase in circulating NE levels in both groups. Increases in heart rate in the presence of ganglionic blockade (+54 +/- 6 beats/min) were less than in the presence of atropine alone (+92 +/- 10 beats/min). Notably, the LV dP/dt and heart rate responses to forskolin were further attenuated by beta-adrenergic receptor blockade in the presence and absence of ganglionic blockade. Morphine also attenuated the increases in both LV dP/dt and plasma NE in response to forskolin. Increases in LV dP/dt in response to NKH-477 (30 micrograms/kg), a water-soluble forskolin derivative, were similar before and after ganglionic blockade (+63 +/- 8 and +51 +/- 10%, respectively). However, in vitro experiments in LV sarcolemmal membrane preparations demonstrated that stimulation of adenylyl cyclase by forskolin and NKH-477 was not affected by beta-adrenergic receptor blockade. These results indicate that in conscious dogs, inotropic and chronotropic effects of forskolin are not only due to direct activation of adenylyl cyclase, but the effects also are mediated by neural mechanisms and potentiated by the prevailing level of sympathetic tone.

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1069: Ejaculatory Disorder Induced by Alpha-Adrenergic Receptor Blockade is not Retrograde Ejaculation

The Journal of Urology ◽

10.1016/s0022-5347(18)35225-x ◽

2005 ◽

Vol 173 (4S) ◽

pp. 290-290 ◽

Cited By ~ 5

Author(s):

Shin-ichi Hisasue ◽

Ryoji Furuya ◽

Naoki Itoh ◽

Ryuichi Kato ◽

Ko Kobayashi ◽

...

Keyword(s):

Adrenergic Receptor ◽

Retrograde Ejaculation ◽

Receptor Blockade ◽

Alpha Adrenergic Receptor ◽

Ejaculatory Disorder ◽

Adrenergic Receptor Blockade

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Effects of chronic alpha-adrenergic receptor blockade on peripheral nerve conduction, hypoxic resistance, polyols, Na(+)-K(+)-ATPase activity, and vascular supply in STZ-D rats

Diabetes ◽

10.2337/diabetes.40.12.1652 ◽

1991 ◽

Vol 40 (12) ◽

pp. 1652-1658 ◽

Cited By ~ 30

Author(s):

N. E. Cameron ◽

M. A. Cotter ◽

K. Ferguson ◽

S. Robertson ◽

M. A. Radcliffe

Keyword(s):

Peripheral Nerve ◽

Atpase Activity ◽

Nerve Conduction ◽

Adrenergic Receptor ◽

Vascular Supply ◽

Receptor Blockade ◽

Alpha Adrenergic Receptor ◽

Hypoxic Resistance ◽

Adrenergic Receptor Blockade

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Differential effects of β-adrenergic receptor blockade in basolateral amygdala or insular cortex on incidental and associative taste learning

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2008.01.004 ◽

2008 ◽

Vol 90 (1) ◽

pp. 54-61 ◽

Cited By ~ 11

Author(s):

Maria Isabel Miranda ◽

Gabriela Rodrı´guez-Garcı´a ◽

Julian V. Reyes-López ◽

Barbara Ferry ◽

Guillaume Ferreira

Keyword(s):

Adrenergic Receptor ◽

Basolateral Amygdala ◽

Insular Cortex ◽

Receptor Blockade ◽

Differential Effects ◽

Adrenergic Receptor Blockade

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Differential effects of β-adrenergic receptor blockade in the medial prefrontal cortex during aversive and incidental taste memory formation

Neuroscience ◽

10.1016/j.neuroscience.2010.04.054 ◽

2010 ◽

Vol 169 (1) ◽

pp. 195-202 ◽

Cited By ~ 11

Author(s):

J. Reyes-López ◽

L. Nuñez-Jaramillo ◽

E. Morán-Guel ◽

M.I. Miranda

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Adrenergic Receptor ◽

Memory Formation ◽

Receptor Blockade ◽

Differential Effects ◽

Adrenergic Receptor Blockade

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Vascular responses after alpha adrenergic receptor blockade

Journal of Clinical Investigation ◽

10.1172/jci105699 ◽

1968 ◽

Vol 47 (1) ◽

pp. 1-9 ◽

Cited By ~ 33

Author(s):

Francois M. Abboud ◽

Phillip G. Schmid ◽

John W. Eckstein

Keyword(s):

Adrenergic Receptor ◽

Receptor Blockade ◽

Vascular Responses ◽

Alpha Adrenergic Receptor ◽

Adrenergic Receptor Blockade

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O2 consumption during exercise in dogs--roles of splenic contraction and alpha-adrenergic vasoconstriction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.251.3.h502 ◽

1986 ◽

Vol 251 (3) ◽

pp. H502-H509 ◽

Cited By ~ 14

Author(s):

J. C. Longhurst ◽

T. I. Musch ◽

G. A. Ordway

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Adrenergic Receptor ◽

Maximal Exercise ◽

Adrenergic Blockade ◽

Receptor Blockade ◽

O2 Consumption ◽

Alpha Adrenergic Receptor ◽

O2 Extraction ◽

Adrenergic Receptor Blockade

To examine the influence of alpha-adrenergic vasoconstriction on the aerobic capacity of dogs, we calculated O2 consumption (VO2) by the Fick method during submaximal and maximal exertion before and during alpha-adrenergic blockade with phentolamine. Regional blood flow was measured with radioactive microspheres. alpha-Adrenergic receptor blockade reduced VO2 by 12.9% during submaximal and 17.9% during maximal exercise. Arterial and venous lactic acid approximately doubled during both levels of stress in the presence of alpha-adrenergic receptor blockade. Calculated VO2 decreased because arteriovenous O2 (A-V)O2 extraction was reduced by 11.6% during submaximal exercise. During maximal exercise a 16.7% decrease in (A-V)O2 extraction and a 5.7% decrease in cardiac output contributed to the decrease in maximal VO2. During both levels of stress, (A-V)O2 extraction was reduced because arterial O2 content was decreased. Since circulating hematocrits during exercise were reduced by alpha-adrenergic receptor blockade (43-38%), we postulate that splenic contraction likely was inhibited. Additionally, distribution of blood flow to skeletal muscle and visceral organs was unaltered by alpha-blockade. To examine the importance of splenic contraction during maximal exercise, we examined hemodynamic and metabolic responses before and after splenectomy. Compared with the spleen-intact condition, splenectomized dogs demonstrated a 12.6% reduction in VO2 as a result of 7.7 and 5.5% reductions in (A-V)O2 extraction and cardiac output, respectively. (A-V)O2 extraction was reduced because arterial O2 content and circulating hematocrit during exercise were decreased. Therefore, in the exercising dog, alpha-adrenergic receptor blockade reduces O2 consumption and causes a shift to anaerobic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

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