The relationship between some beta-adrenergic mediated responses and plasma concentrations of adrenaline and cyclic AMP in man

1990 ◽  
Vol 122 (1) ◽  
pp. 115-120 ◽  
Author(s):  
E. K. Philipsen ◽  
J. Myhre ◽  
S. Larsen ◽  
M. Damkjær Nielsen ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Plasma Concentrations ◽  
Beta Agonist ◽  
Beta Blockade ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Plasma Adrenaline ◽  
Beta Adrenoceptor ◽  
Adrenaline Infusion ◽  
The Relationship

Abstract To test the hypothesis that increments in plasma cyclic AMP during beta-adrenergic stimulation reflect integrated second messenger function of the tissues activated by the angonist, graded adrenaline infusion resulting in plasma adrenaline concentrations within the physiological range was performed in 8 healthy subjects with and without concomitant beta-adrenoceptor blockade by iv propranolol. A significant correlation was found between increments in plasma adrenaline and plasma cyclic AMP in the experiments without beta-blockade; during concomitant beta-blockade the increase in plasma cyclic AMP concentrations at low adrenaline infusion rates was prevented, whereas a small increase in cyclic AMP was found at high adrenaline infusion rates, probably owing to incomplete beta-receptor blockade. Likewise, the adrenaline-induced increments in blood substrates (glucose, lactate, glycerol and betahydroxy butyric acid) were significantly reduced but not completely prevented by beta-blockade. We conclude that an altered relationship between beta-agonist concentrations and plasma cyclic AMP may provide evidence for the existence of differences in beta-adrenergic sensitivity in man.

Depressed [Ca2+]i responses to isoproterenol and cAMP in isolated cardiomyocytes from experimental diabetic rats

1994 ◽  
Vol 266 (6) ◽  
pp. H2334-H2342 ◽  
Author(s):  
Z. Yu ◽  
G. A. Quamme ◽  
J. H. McNeill
Keyword(s):  
Diabetic Rats ◽  
Beta Agonist ◽  
Diabetic Rat ◽  
Dependent Manner ◽  
Adrenergic Stimulation ◽  
Protein Activity ◽  
Concentration Dependent Manner ◽  
Beta Adrenergic ◽  
Beta Adrenoceptor ◽  
Diabetic Myocardium

Experimentally, diabetic rat hearts are characterized by diminished responses to beta-adrenergic stimulation. Among the aberrant responses are diminished beta-adrenoceptor number and depressed contractile protein activity. In this study, intracellular Ca2+ concentration ([Ca2+]i) was determined by microfluorescence in response to beta-adrenergic stimulation to understand the basis for the changes in the beta-adrenergic pathway in diabetic myocardium. In quiescent myocytes, isoproterenol caused a decrease in [Ca2+]i, which was blocked by timolol and thapsigargin. This suggests that the beta-agonist-induced [Ca2+]i changes are mediated, in part, by sarcoplasmic reticulum Ca-adenosinetriphosphatase. Diabetic myocytes showed a blunted response to isoproterenol, which was reversed by insulin treatment. In electrically stimulated myocytes, isoproterenol and 8-bromo-adenosine 3',5'-cyclic monophosphate (cAMP) increased [Ca2+]i and contraction in a concentration-dependent manner. Electrically stimulated diabetic myocytes demonstrated a depressed maximum [Ca2+]i response to isoproterenol and 8-bromo-cAMP without a change in sensitivity. These data suggest that in addition to alterations in beta-adrenoceptor function there are postreceptor defects in diabetic myocardium that may impair the regulation of [Ca2+]i in diabetic myocardium.

Effects of beta-adrenergic agents in lungs of normal and air-embolized awake sheep

1988 ◽  
Vol 64 (6) ◽  
pp. 2647-2652 ◽  
Author(s):  
M. R. Bonsignore ◽  
E. H. Jerome ◽  
P. L. Culver ◽  
P. M. Dodek ◽  
N. C. Staub
Keyword(s):  
Air Embolism ◽  
Lymph Flow ◽  
Beta Agonist ◽  
Beta Blockade ◽  
Base Line ◽  
Pulmonary Hemodynamics ◽  
Beta Adrenergic ◽  
Adrenergic Agents ◽  
Venous Air Embolism ◽  
Lung Lymph

It is unclear whether beta-adrenergic agonists or antagonists affect lung liquid and protein exchange by changing pulmonary hemodynamics or microvascular leakiness. In 23 unanesthetized, instrumented sheep with long-term lung lymph fistulas, we assessed the effect of the beta-agonist terbutaline or the beta-antagonists propranolol, nadolol, and atenolol, all infused intravenously, on lung lymph flow under base-line conditions and during the acute lung injury caused by 4 h of venous air embolism. Under base-line conditions, neither beta-stimulation nor blockade had any effect. During air embolism, terbutaline decreased pulmonary vascular resistance and lymph flow by 25%. Propranolol and nadolol (non-selective beta 1,beta 2-antagonists) but not atenolol (selective beta 1-antagonist) also decreased lymph flow by 22% on average. We favor the more conservative (hemodynamic) over the more liberal (altered permeability) explanation for our results. First, beta-stimulation clearly caused vasodilation, which lowered the pulmonary microvascular pressure at the site of injury. beta-blockade caused changes similar to alpha-stimulation (J. Appl. Physiol. 62: 2147–2153, 1987). We therefore interpret the beta-blockade as unmasking pulmonary arterial alpha-receptors stimulated by the air-embolism injury, thus allowing vasoconstriction upstream to the site of injury. We do not believe the explanation of the beta-agent effects requires any modulation of lung microvascular leakiness by beta-adrenergic agents.

scholarly journals High‐Dose Glucagon Has Hemodynamic Effects Regardless of Cardiac Beta‐Adrenoceptor Blockade: A Randomized Clinical Trial

2020 ◽  
Vol 9 (21) ◽  
Author(s):  
Kasper M. Petersen ◽  
Søren Bøgevig ◽  
Troels Riis ◽  
Niklas W. Andersson ◽  
Kim P. Dalhoff ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Concentrations ◽  
Random Order ◽  
Beta Blockade ◽  
High Dose ◽  
Clinical Effects ◽  
Hemodynamic Effects ◽  
Unique Identifier ◽  
Beta Adrenoceptor ◽  
Randomized Crossover Study

Background Intravenous high‐dose glucagon is a recommended antidote against beta‐blocker poisonings, but clinical effects are unclear. We therefore investigated hemodynamic effects and safety of high‐dose glucagon with and without concomitant beta‐blockade. Methods and Results In a randomized crossover study, 10 healthy men received combinations of esmolol (1.25 mg/kg bolus+0.75 mg/kg/min infusion), glucagon (50 µg/kg), and identical volumes of saline placebo on 5 separate days in random order (saline+saline; esmolol+saline; esmolol+glucagon bolus; saline+glucagon infusion; saline+glucagon bolus). On individual days, esmolol/saline was infused from −15 to 30 minutes. Glucagon/saline was administered from 0 minutes as a 2‐minute intravenous bolus or as a 30‐minute infusion (same total glucagon dose). End points were hemodynamic and adverse effects of glucagon compared with saline. Compared with saline, glucagon bolus increased mean heart rate by 13.0 beats per minute (95% CI, 8.0–18.0; P <0.001), systolic blood pressure by 15.6 mm Hg (95% CI, 8.0–23.2; P =0.002), diastolic blood pressure by 9.4 mm Hg (95% CI, 6.3–12.6; P <0.001), and cardiac output by 18.0 % (95% CI, 9.7–26.9; P =0.003) at the 5‐minute time point on days without beta‐blockade. Similar effects of glucagon bolus occurred on days with beta‐blockade and between 15 and 30 minutes during infusion. Hemodynamic effects of glucagon thus reflected pharmacologic glucagon plasma concentrations. Glucagon‐induced nausea occurred in 80% of participants despite ondansetron pretreatment. Conclusions High‐dose glucagon boluses had significant hemodynamic effects regardless of beta‐blockade. A glucagon infusion had comparable and apparently longer‐lasting effects compared with bolus, indicating that infusion may be preferable to bolus injections. Registration Information URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03533179.

Cyclic AMP Second-Messenger Signal Amplification in Depression

1988 ◽  
Vol 152 (5) ◽  
pp. 665-669 ◽  
Author(s):  
Richard P. Ebstein ◽  
Bernard Lerer ◽  
Baruch Shapira ◽  
Zecharia Shemesh ◽  
Daniel G. Moscovich ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Signal Amplification ◽  
Antidepressant Treatment ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Late Night ◽  
Depressed Patients ◽  
Cyclic Amp Accumulation ◽  
Significant Clinical Improvement ◽  
Age And Sex

Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.

Beta-adrenergic effects on left ventricular filling: influence of aging and exercise training

1994 ◽  
Vol 77 (6) ◽  
pp. 2522-2529 ◽  
Author(s):  
J. R. Stratton ◽  
W. C. Levy ◽  
R. S. Schwartz ◽  
I. B. Abrass ◽  
M. D. Cerqueira
Keyword(s):  
Heart Rate ◽  
Endurance Training ◽  
Left Ventricular ◽  
Beta Agonist ◽  
Diastolic Filling ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
End Diastolic Volume ◽  
Before And After ◽  
Ventricular Filling

Reduced heart rate and contractile responses to beta-agonist stimulation characterize normal cardiac aging, but whether diastolic responses also decline with aging has not been determined in humans. Diastolic filling responses to isoproterenol were determined in 13 older (60–82 yr) and 11 young (24–32 yr) healthy men before and after endurance training. Filling rates were expressed in three ways: 1) normalized to end-diastolic volume per second, 2) normalized to stroke volume per second, and 3) as absolute milliliters of blood (ml.s-1.m-2). Peak early filling rates by all methods were reduced at rest and all isoproterenol doses with aging (all P < 0.0001 for old vs. young), whereas peak atrial filling rates were increased with aging. During isoproterenol, both peak early and peak atrial filling rates increased significantly (all P < 0.01); the increase in filling rates with isoproterenol was not different with aging (all NS for old vs. young x dose). Endurance training did not augment diastolic filling responses to isoproterenol. Although diastolic filling rates at rest are markedly altered by aging, diastolic filling responses to isoproterenol are not reduced with aging. Thus the age-associated declines in heart rate, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol do not extend to diastolic filling responses.

scholarly journals Inhibition by calcium ions of adenosine cyclic monophosphate formation in sealed pigeon erythrocyte ‘ghosts’. A study using the photoprotein obelin

1978 ◽  
Vol 176 (1) ◽  
pp. 53-66 ◽  
Author(s):  
A K Campbell ◽  
R L Dormer
Keyword(s):  
Cyclic Amp ◽  
Initial Rate ◽  
Ionophore A23187 ◽  
Erythrocyte Ghosts ◽  
Adrenergic Agonists ◽  
Intact Cells ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
The Relationship ◽  
Stimulation Of

1. Sealed pigeon erythrocyte ‘ghosts’ were prepared containing ATP and the Ca2+-activated photoprotein obelin to investigate the relationship cyclic AMP formation and internal free Ca2+. 2. The ‘ghosts’ were characterized by (a) morphology (optical and electron microscopy), (b) composition (haemoglobin, K+, Na+, Mg2+, ATP, obelin), (c) permeability to Ca2+, assessed by obelin luminescence and (d) hormone sensitivity (the effect of beta-adrenergic agonists and antagonists on cyclic AMP formation). 3. The effect of osmolarity at haemolysis and ATP at resealing on these parameters was investigated. 4. Sealed ‘ghosts’, containing approx. 2% of original haemoglobin, 150mM-K+, 0.5MM-ATP, 10(3)–10(4) obelin luminescence counts/10(6) ‘ghosts’, which were relatively impermeable to Ca2+ and in which cyclic AMP formation was stimulated by beta-adrenergic agonists over a concentration range similar to that for intact cells, could be prepared after haemolysis in 6mM-NaCl3mM-MgCl2/50mM-Tes, pH7, and resealing for 30min at 37 degrees C in the presence of ATP and 150mM-KCl. 5. The initial rate of adrenaline-stimulated cyclic AMP formation in these ‘ghosts’ was 30–50% of that in intact cells and was inhibited by the addition of extracellular Ca2+. Addition of Ca2+ to the ‘ghosts’ resulted in a stimulation of obelin luminescence, indicating an increase in internal free Ca2+ under these conditions. 6. The ionophore A23187 increased the rate of obelin luminescence in the ‘ghosts’ and also inhibited the adrenaline-stimulated increase in cyclic AMP. 7. The effect of ionophore A23187 on obelin luminescence and on cyclic AMP formation in the ‘ghosts’ was markedly decreased by sealing EGTA inside the ‘ghosts’. 8. It was concluded that cyclic AMP formation inside sealed pigeon erythrocyte ‘ghosts’ could be inhibited by more than 50% by free Ca2+ concentrations in the range 1–10 micrometer.

Defining the volume dependence of multiple K flux pathways of trout red blood cells

1997 ◽  
Vol 272 (4) ◽  
pp. C1099-C1111 ◽  
Author(s):  
M. Berenbrink ◽  
Y. R. Weaver ◽  
A. R. Cossins
Keyword(s):  
Ionic Strength ◽  
Red Blood Cells ◽  
Ammonium Chloride ◽  
Blood Cells ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Graded Responses ◽  
Volume Dependence ◽  
Volume Sensitivity ◽  
The Relationship

The volume sensitivity of different K flux pathways has been determined in trout red blood cells subjected to volume perturbation. Gentle hyposmotic swelling induced a K influx in a Cl-containing saline but not in NO3- or methanesulfonate (MeSF)-containing salines, consistent with the activation of a Cl-dependent flux. Extreme hyposmotic swelling led to larger K fluxes in all salines but with reduced anion discrimination of the Cl-dependent flux. In contrast to these graded responses, isosmotic swelling using ammonium chloride or beta-adrenergic stimulation activated only Cl-dependent fluxes in an all-or-none fashion. The relationship between the hyposmotically and isosmotically induced pathways was studied by coactivation using either ammonium chloride or isoproterenol with anisosmotic treatment. Cells in ammonium chloride-containing hyposmotic salines showed no additive K flux over that induced by hyposmotic treatment alone, indicating that the isosmotically induced Cl-dependent flux was identical to the hyposmotically induced Cl-dependent flux. However, cells coactivated by hyposmotic and beta-adrenergic treatment showed a small Cl-dependent flux in addition to that induced by hyposmotic treatment alone. This small third component was unaffected by anisosmotic treatment. We conclude that the major Cl-dependent and Cl-independent K flux pathways are distinct and separate and that the former has an anion dependence that varies with cell volume and a volume sensitivity that varies with ionic strength.

Beta-adrenergic blockade and training in human subjects: effects on muscle metabolic capacity

1984 ◽  
Vol 247 (3) ◽  
pp. E305-E311 ◽  
Author(s):  
J. Svedenhag ◽  
J. Henriksson ◽  
A. Juhlin-Dannfelt
Keyword(s):  
Placebo Group ◽  
Citrate Synthase ◽  
Human Subjects ◽  
Capillary Density ◽  
Beta Blockade ◽  
Adrenergic Blockade ◽  
Mitochondrial Enzymes ◽  
Beta Adrenergic ◽  
Beta Adrenoceptor ◽  
Cyt C

Sixteen male subjects (20–31 yr) trained for 8 wk on cycle ergometers. Eight of the subjects were treated during the training period with the beta-adrenoceptor blocker propranolol (160 mg/day). During all pre-and posttraining tests, subjects were uninfluenced by the medication. Training-induced increases in VO2max and decreases in blood lactate and norepinephrine concentrations at submaximal exercise were not different between the beta-blockade and the placebo groups. The activities of the mitochondrial enzymes citrate synthase (CS), succinate dehydrogenase (SDH), cytochrome c oxidase (Cyt-c-ox), and 3-hydroxyacyl-CoA dehydrogenase (HAD) in the quadriceps femoris muscle increased significantly (P less than 0.01) with training (beta-blockade group, +47, +33, +38, and 22%; placebo group, +75, 70, +87, and +63%, respectively). Cyt-c-ox and HAD increased significantly more in the placebo group than in the beta-blockade group, while a tendency to an increase was noted for SDH. Muscle capillary density increased similarly (+17–19%) with training in the two groups (P less than 0.01). In conclusion, subjects training under the influence of a therapeutic level of beta-adrenergic blockade show marked increases in both the respiratory capacity and the capillary supply of the engaged skeletal muscles. However, the increase in muscle mitochondrial enzymes may be less apparent than in the normal state.

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