Ionic mechanisms responsible for the antiarrhythmic action of dehydroevodiamine in guinea‐pig isolated cardiomyocytes

Loh, Shih‐Hurng; Lee, An‐Rong; Lin, Cheng‐I

doi:10.1111/j.1476-5381.1992.tb14368.x

Cited by 27 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the past decades, evodiamine, the main ingredient of the bioactive components of this fruit, had been found to account for the antiarrhythmic or hypotensive effect by prolonging the action-potential duration in cardiac cells or by inducing vascular relaxation (49,50). Notably, we recently demonstrated that evodiamine can induce an increase in NO bioavailability in ECs and confer protection from atherosclerosis in ApoE-deficient mice (8).…”

Section: A M P K I N T R P V 1 -M E D I a T E D E N O S A C T I Vmentioning

confidence: 99%

Implication of AMP-Activated Protein Kinase in Transient Receptor Potential Vanilloid Type 1-Mediated Activation of Endothelial Nitric Oxide Synthase

Ching

Chen

et al. 2012

Mol Med

View full text Add to dashboard Cite

We investigated whether AMP-activated protein kinase (AMPK), a multifunctional regulator of energy homeostasis, is involved in transient receptor potential vanilloid type 1 (TRPV1)-mediated activation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) and mice. In ECs, treatment with evodiamine, the activator of TRPV1, increased the phosphorylation of AMPK, acetyl-CoA carboxylase (ACC) and eNOS, as revealed by Western blot analysis. Inhibition of AMPK activation by compound C or dominant-negative AMPK mutant abrogated the evodiamine-induced increase in phosphorylation of AMPK and eNOS and NO bioavailability, as well as tube formation in ECs. Immunoprecipitation and two-hybrid analysis demonstrated that AMPK mediated the evodiamine-induced increase in the formation of a TRPV1-eNOS complex. Additionally, TRPV1 activation by evodiamine increased the phosphorylation of AMPK and eNOS in aortas of wild-type mice but did not activate eNOS in aortas of TRPV1-deficient mice. In mice, inhibition of AMPK activation by compound C markedly decreased evodiamine-evoked angiogenesis in matrigel plugs and in a hind-limb ischemia model. Moreover, evodiamine-induced phosphorylation of AMPK and eNOS in aortas of apolipoprotein E-deficient (ApoE -/-) mice was abrogated in TRPV1-deficient ApoE -/-mice. In conclusion, TRPV1 activation may trigger AMPK-dependent signaling, which leads to enhanced activation of AMPK and eNOS and retarded development of atherosclerosis.

show abstract

Section: A M P K I N T R P V 1 -M E D I a T E D E N O S A C T I Vmentioning

confidence: 99%

Implication of AMP-Activated Protein Kinase in Transient Receptor Potential Vanilloid Type 1-Mediated Activation of Endothelial Nitric Oxide Synthase

Ching

Chen

et al. 2012

Mol Med

View full text Add to dashboard Cite

show abstract

“…At 1 ÌM and above, DeHE also inhibits I Ca . Thus, a low concentration of DeHE may depress arrhythmias in Ca 2+ -overloaded myocytes through its inhibitory action on I Na (rather than on I Ca ), presumably by decreasing the transmembrane Na + gradient and therefore decreasing [Ca 2+ ] i by enhancing Ca 2+ extrusion [68].…”

Section: Electrical Manifestations Of Ca 2+ Overloadmentioning

confidence: 99%

Calcium Overload and Cardiac Function

Vassalle

Chen

2004

J Biomed Sci

View full text Add to dashboard Cite

The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca²⁺ may increase in different structures [e.g. sarcoplasmic reticulum (SR), cytoplasm and mitochondria] to an excessive level which induces electrical and mechanical abnormalities in cardiac tissues. The electrical manifestations of Ca²⁺ overload include arrhythmias caused by oscillatory (V_os) and non-oscillatory (V_ex) potentials. The mechanical manifestations include a decrease in force of contraction, contracture and aftercontractions. The underlying mechanisms involve a role of Na⁺ in electrical abnormalities as a charge carrier in the Na⁺-Ca²⁺ exchange and a role of Ca²⁺ in mechanical toxicity. Ca²⁺ overload may be induced by an increase in [Na⁺]_i through the inhibition of the Na⁺-K⁺ pump (e.g. toxic concentrations of digitalis) or by an increase in Ca²⁺ load (e.g. catecholamines). The Ca²⁺ overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca²⁺ overload than myocardial fibers, possibly because of their greater Na⁺ load. If the SR is predominantly Ca²⁺ overloaded, V_os and fast discharge are induced through an oscillatory release of Ca²⁺ in diastole from the SR; if the cytoplasm is Ca²⁺ overloaded, the non-oscillatory V_ex tail is induced at negative potentials. The decrease in contractile force by Ca²⁺ overload appears to be associated with a decrease in high energy phosphates, since it is enhanced by metabolic inhibitors and reduced by metabolic substrates. The ionic currents I_os and I_ex underlie V_os and V_ex, respectively, both being due to an electrogenic extrusion of Ca²⁺ through the Na⁺-Ca²⁺ exchange. I_os is an oscillatory current due to an oscillatory release of Ca²⁺ in early diastole from the Ca²⁺-overloaded SR, and I_ex is a non-oscillatory current due to the extrusion of Ca²⁺ from the Ca²⁺-overloaded cytoplasm. I_os and I_ex can be present singly or simultaneously. An increase in [Ca²⁺]_i appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, [Ca²⁺]_i may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca²⁺-overloaded cardiac cells by decreasing the inhibition of the Na⁺-K⁺ pump by Ca²⁺, thereby leading to a reduction in Ca²⁺ overload and to an increase in force of contraction.

show abstract

“…4a) [37]), transient inward currents, aftercontractions and other signs of intracellular Ca 2+ overload in cardiac tissues [8,18] and cardiomyocytes [31].…”

Section: Af Induced By High [Ca 2+ ] and Low [K + ] Superfusatementioning

confidence: 99%

“…The specific aims were to investigate whether (1) myopathic atria respond abnormally to ACh; (2) ACh-induced fast rhythms occur more frequently in diseased atria; (3) AChinduced fast rhythms require the activation of muscarinic receptors and are Na + -dependent; (4) ACh-induced fast rhythms are prevented by reducing the mass of the right atrium, and (5) the increase in Na + and Ca 2+ load induced by means of fast-pacing [7,11] [9,31] induces abnormal rhythms more frequently in myopathic atria. A preliminary report has been presented at a scientific meeting [28].…”

Section: Introductionmentioning

confidence: 99%

Reentrant Tachyarrhythmias in Right Atria of Cardiomyopathic versus Healthy Syrian Hamster

et al. 1999

View full text Add to dashboard Cite

We studied the role of acetylcholine (ACh) and calcium overload in the induction of atrial flutter or atrial fibrillation (AF) in right atria from 34 normal male Syrian hamsters (F1B) and 33 cardiomyopathic Syrian hamsters (BIO 14.6) associated with focal myocardial necrosis. Action potential (AP) was recorded with conventional microelectrode techniques and twitch force by a transducer. ACh (0.1, 1 and 10 μM) induced high-frequency AF (around 33 Hz) along with tension oscillations and contracture in 7 of 12 normal hamster atria. These effects of ACh were abolished by tetrodotoxin or quinidine as well as by atropine. In contrast, ACh induced AF only in 1 of 12 myopathic atria. In both normal and myopathic atria, ACh induced similar changes in AP duration, spontaneous rate and force. The effects of calcium overload were tested by means of a high [Ca²⁺]_o (8.1 mM) low [K⁺]_o (1 mM) solution in another series of experiments. This solution also induced incidence of AF higher in normal (10/12) than in myopathic atria (4/12). The calcium load was also increased by high-frequency pacing (32 Hz for 3 or 30 s): AF occurred in normal atria (5/8), but not in myopathic atria (0/8). Measurement of the refractory period revealed a longer refractory period in myopathic than in control atria. We concluded that the lower incidence of AF in myopathic atria was probably due to their longer refractory period and the associated focal myocardial necrosis which then hindered the establishment of such a reentrant rhythm.

show abstract

Ionic mechanisms responsible for the antiarrhythmic action of dehydroevodiamine in guinea‐pig isolated cardiomyocytes

Cited by 27 publications

References 26 publications

Implication of AMP-Activated Protein Kinase in Transient Receptor Potential Vanilloid Type 1-Mediated Activation of Endothelial Nitric Oxide Synthase

Implication of AMP-Activated Protein Kinase in Transient Receptor Potential Vanilloid Type 1-Mediated Activation of Endothelial Nitric Oxide Synthase

Calcium Overload and Cardiac Function

Reentrant Tachyarrhythmias in Right Atria of Cardiomyopathic versus Healthy Syrian Hamster

Contact Info

Product

Resources

About