Effects of the ACE Inhibitor, Perindoprilat, and of Angiotensin II on the Transient Inward Current of Guinea Pig Ventricular Myocytes

Enous, R.; Wa, Coetzee; Lh, Opie

doi:10.1097/00005344-199201000-00003

Cited by 13 publications

(6 citation statements)

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“…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

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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.

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Section: Introductionmentioning

confidence: 99%

Reentrant Tachyarrhythmias in Right Atria of Cardiomyopathic versus Healthy Syrian Hamster

et al. 1999

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“…Furthermore, ANG II inhibits the Ca 2ϩ -activated K ϩ current in vascular smooth muscle cells (51) and the delayed rectifier K ϩ currents in heart and smooth muscle (11). ANG II has been shown to alter cardiac Cl Ϫ conductance and the transient outward current (I to ) (17,39,43,60,61).Connexins are transmembrane proteins that assemble as dodecamers and form low-resistance conductive pathways between cardiac myocytes known as gap junctions. The three most prominent cardiac connexins are connexin 40 (Cx40), connexin 43 (Cx43), and connexin 45 (Cx45).…”

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confidence: 99%

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confidence: 99%

Cardiac-restricted angiotensin-converting enzyme overexpression causes conduction defects and connexin dysregulation

Kasi

Xiao

Shang

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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(RAS) system activation is associated with an increased risk of sudden death. Previously, we used cardiac-restricted angiotensin-converting enzyme (ACE) overexpression to construct a mouse model of RAS activation. These ACE 8/8 mice die prematurely and abruptly. Here, we have investigated cardiac electrophysiological abnormalities that may contribute to early mortality in this model. In ACE 8/8 mice, surface ECG voltages are reduced. Intracardiac electrograms showed atrial and ventricular potential amplitudes of 11% and 24% compared with matched wild-type (WT) controls. The atrioventricular (AV), atrioHisian (AH), and Hisian-ventricular (HV) intervals were prolonged 2.8-, 2.6-, and 3.9-fold, respectively, in ACE 8/8 vs. WT mice. Various degrees of AV nodal block were present only in ACE 8/8 mice. Intracardiac electrophysiology studies demonstrated that WT and heterozygote (HZ) mice were noninducible, whereas 83% of ACE 8/8 mice demonstrated ventricular tachycardia with burst pacing. Atrial connexin 40 (Cx40) and connexin 43 (Cx43) protein levels, ventricular Cx43 protein level, atrial and ventricular Cx40 mRNA abundances, ventricular Cx43 mRNA abundance, and atrial and ventricular cardiac Na ϩ channel (Scn5a) mRNA abundances were reduced in ACE 8/8 compared with WT mice. ACE 8/8 mice demonstrated ventricular Cx43 dephosphorylation. Atrial and ventricular L-type Ca 2ϩ channel, Kv4.2 K ϩ channel ␣-subunit, and Cx45 mRNA abundances and the peak ventricular Na ϩ current did not differ between the groups. In isolated heart preparations, a connexin blocker, 1-heptanol (0.5 mM), produced an electrophysiological phenotype similar to that seen in ACE 8/8 mice. Therefore, cardiac-specific ACE overexpression resulted in changes in connexins consistent with the phenotype of low-voltage electrical activity, conduction defects, and induced ventricular arrhythmia. These results may help explain the increased risk of arrhythmia in states of RAS activation such as heart failure.peptidyl-dipeptidase A; angiotensin II; heart block ARRHYTHMIC SUDDEN DEATH is a common terminal event in various cardiomyopathies and end-stage heart failure. Upregulation of the renin-angiotensin system (RAS) has been implicated in risk of sudden death in these conditions. A critical component of this system is angiotensin-converting enzyme (ACE), which produces the eight-amino acid peptide angiotensin II (ANG II), a major effector peptide of the RAS. In humans, increased ANG II levels are associated with an increased risk of arrhythmia (2), which is reduced by use of ACE inhibitors or ANG II receptor blockers (4,13,20,23,27,30,49).A number of ion-handling protein changes have been posited to underlie the increase in risk of arrhythmia in states of RAS activation, and ANG II is known to act on a number of these proteins (3, 41). For example, ANG II has been implicated in Na ϩ -K ϩ pump regulation (24). Furthermore, ANG II inhibits the Ca 2ϩ -activated K ϩ current in vascular smooth muscle cells (51) and the delayed rectifier K ϩ currents in heart and...

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“…To evaluate the depressant effects of DeHE on triggered activity, the cells were bathed in low-K (1 mM), high-Ca (9 mM) HEPES solution plus 2 JiM strophanthidin. The cells were dialysed with a pipette solution containing (in mM): KCl 120, Na2ATP 5, HEPES 10, EGTA 0.5, MgCl2 1, CaC12 0.01 and pH 7.2 (see Enous et al, 1990). The holding potential was set to -44 mV.…”

Section: Methodsmentioning

confidence: 99%

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

Loh

Lee

Lin

1992

British J Pharmacology

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1 Dehydroevodiamine alkaloid (DeHE), an active ingredient of a Chinese herbal medicine Wu-Chu-Yu (Evodiae frutus), has been shown to decrease aterial blood pressure in experimental animals and prolong action potential duration in cardiac cells. The aim of the present study was to explore the ionic basis of its possible antiarrhythmic effects. 2 Guinea-pig atrial and ventricular myocytes were isolated enzymatically and the ionic currents were recorded under whole-cell patch-clamp with single suction pipettes. 3 DeHE at a concentration of 0.1 jAM inhibited reversibly the time-dependent outward K current (delayed rectifier, Ik) and the Na-dependent inward current ('Na). 4 In low-K (1 mM) and high-Ca (9 mM) solution, DeHE also depressed the delayed afterdepolarizations (DAD) and the transient inward current (Ij) induced by 2 gM strophanthidin. On the other hand, DeHE occasionally induced early afterdepolarizations and slow response action potentials at a depolarized level. 5 At higher concentrations (1 jiM and above), the L-type Ca current (ICaL) was moderately inhibited. 6 The present findings indicate that DeHE may depress triggered arrhythmias in Ca-overloaded guinea-pig cardiac myocytes through its inhibitory actions on INa, Iti and, to a smaller extent, ICa. DeHE may also exert class III antiarrhythmic effect through a reduction of outward K currents (Ik) across the sarcolemma.

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Effects of the ACE Inhibitor, Perindoprilat, and of Angiotensin II on the Transient Inward Current of Guinea Pig Ventricular Myocytes

Cited by 13 publications

References 0 publications

Reentrant Tachyarrhythmias in Right Atria of Cardiomyopathic versus Healthy Syrian Hamster

Reentrant Tachyarrhythmias in Right Atria of Cardiomyopathic versus Healthy Syrian Hamster

Cardiac-restricted angiotensin-converting enzyme overexpression causes conduction defects and connexin dysregulation

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

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