Cardioprotective role of chunglijagam-tang, a Korean herbal medicine, against β-adrenergic receptor stimulation-induced myocardial toxicity

2019 ◽  
Vol 6 ◽  
pp. S138-S139
Author(s):  
Ho-Sung Lee ◽  
Seung Hoon Lee ◽  
Dal-Seok Oh
2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Stephen W Luckey ◽  
Nathan McLaughlin ◽  
Sherilynn Soo

Exercise training protects the heart against the adverse effects of cardiovascular disease. Recent studies have identified a number of cardiac adaptations including the activation of hypertrophic signaling pathways unique to exercise. However, the underlying mechanisms by which exercise confers cardioprotection are not entirely understood. This study aims to fill this gap by examining the role of voluntary exercise in the context of chronic β-adrenergic receptor stimulation. To do this, we developed a novel experimental model in which nine-week-old female and male CB6F1 hybrid mice were subjected to 5 weeks of voluntary wheel running (EX) or housed under sedentary conditions (SED). For the final two weeks, mice were administered either vehicle (VEH) or isoproterenol (ISO, 30mg/kg/day) via an osmotic pump. As expected, we found that ISO significantly increased heart size in sedentary females and males (SED+ISO) compared to sedentary mice receiving VEH (SED+VEH). Consistent with previously published data, exercise capacity was also greater in females compared to males with regards to running duration and distance regardless of the experimental group. While exercise capacity was not affected by the administration of VEH, mice receiving ISO (EX+ISO) exercised significantly less. Cardiac growth in EX+VEH mice was significantly increased in both females and males compared to their respective SED+VEH counterparts. Importantly, EX+ISO females and males have significantly larger hearts than their respective SED+ISO cohorts. Moreover, EX+ISO mice also exhibited greater increases in cardiac size as compared to their respective EX+VEH counterparts. Thus, we conclude that there appears to be an additive effect of voluntary exercise and ISO administration in both females and males in terms of cardiac growth. These preliminary data are in contrast to previously published data which found that controlled exercise programs reduced cardiac hypertrophy under conditions of chronic β-adrenergic receptor stimulation. We are currently investigating the processes that lead to the larger heart sizes in the EX+ISO mice and aim to better understand the underlying mechanisms of exercise-mediated cardioprotection.


The Lancet ◽  
1968 ◽  
Vol 292 (7581) ◽  
pp. 1264-1266 ◽  
Author(s):  
RichardJ. Cohen ◽  
StephenE. Epstein ◽  
LawrenceS. Cohen ◽  
LewisH. Dennis

1997 ◽  
Vol 273 (4) ◽  
pp. H1669-H1676 ◽  
Author(s):  
Livia C. Hool ◽  
Robert D. Harvey

The role of β1- and β2-adrenergic receptor stimulation in modulating adenosine 3′,5′-cyclic monophosphate (cAMP)-regulated Cl− and Ca2+ currents was investigated with use of guinea pig ventricular myocytes. Activation of the Cl− current by the nonselective β-receptor agonist isoproterenol (Iso) was not affected by the β2-receptor antagonist ICI-118,551 (ICI), but it was blocked by the β1-receptor antagonist atenolol. The inability of β2-receptor stimulation to activate the Cl− current was confirmed by the lack of response to the selective β2-receptor agonists salbutamol and zinterol. Responses to β2-adrenergic receptor stimulation were also looked for in pertussis toxin (PTX)-treated myocytes because PTX increases the sensitivity of responses to Iso, and PTX has been reported to increase the responsiveness to β2- but not β1-receptor stimulation. PTX treatment increased the sensitivity of the Cl− current to activation by Iso in the presence of ICI, indicating that PTX increases β1-receptor responsiveness. PTX treatment also resulted in the ability of salbutamol to activate the Cl− current. However, the response to salbutamol was blocked by atenolol but not by appropriate concentrations of ICI, suggesting that salbutamol was activating β1-receptors. These results indicate that PTX treatment increases the sensitivity to β1-receptor stimulation, without affecting β2-responsiveness. To verify that the lack of response to β2-receptor stimulation was not unique to the Cl− current, the effects of β2-receptor agonists on the L-type Ca2+current were also examined. The Ca2+ current was only affected by high concentrations of zinterol or salbutamol, and such responses were blocked by atenolol, but not by ICI, suggesting that activation of β1-receptors was involved. These results indicate that β1- but not β2-adrenergic receptor stimulation plays an important role in modulating the cAMP-regulated Cl− and Ca2+ currents in guinea pig ventricular myocytes.


1993 ◽  
Vol 264 (4) ◽  
pp. G708-G717 ◽  
Author(s):  
T. K. Smith ◽  
S. M. Ward ◽  
L. Zhang ◽  
I. L. Buxton ◽  
W. T. Gerthoffer ◽  
...  

The effects of beta-adrenergic receptor stimulation on the electrical and mechanical activity of canine colonic circular muscles were compared with forskolin (Fsk), a known stimulator of adenylate cyclase. The actions of isoproterenol (Iso) were mediated by beta 2-receptors. Iso and Fsk increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels in both the presence and absence of acetylcholine (ACh), whereas ACh (0.3 microM) alone reduced cAMP levels. These agents caused inhibition of spontaneous and ACh-induced contractions. Inhibition was associated with a reduction in the amplitude and duration of electrical slow waves recorded near the submucosal border. Near the myenteric border, Iso and Fsk hyperpolarized the membrane by up to 30 mV and changed the pattern of electrical rhythmicity. These effects were mimicked by 8-bromo-cAMP (1-3 mM). Contractile inhibition with Fsk and Iso was associated with a decrease in the amplitude and duration of Ca2+ transients measured with fura-2 fluorescence. cAMP (10-300 microM) reduced the Ca2+ sensitivity of the contractile apparatus in muscles permeabilized with staphylococcal alpha-toxin. The actions of Iso appear linked to cAMP. We hypothesize that cAMP produces relaxation both by modulation of membrane ionic channels with a consequent decline in the entry of Ca2+ as well as through a decrease in the sensitivity of the contractile apparatus to Ca2+.


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