Abstract
BackgroundAtrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. However, the role of AVP in HF-induced AF still remains unclear. Pulmonary veins (PVs) are central in the genesis of AF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms.MethodsPatch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, Ca2+ homeostasis, and Ca2+ regulatory proteins in isolated rabbit single PV cardiomyocytes incubated with and without AVP (1 μM), OPC 21268 (0.1 μM, AVP V1 antagonist), or OPC 41061 (10 nM, AVP V2 antagonist) for 4–6 h.ResultsAVP (0.1 and 1 μM)-treated PV cardiomyocytes had a faster beating rate (108 to 152%) than the control cells. AVP (1 μM) treated PV cardiomyocytes had higher late sodium (Na+) and Na+/Ca2+ exchanger (NCX) currents than control PV cardiomyocytes. AVP (1 μM) treated PV cardiomyocytes had smaller Ca2+i transients, and sarcoplasmic reticulum (SR) Ca2+ content as well as higher Ca2+ leak. However, combined AVP (1 μM) and OPC 21268 (0.1 μM) treated PV cardiomyocytes had a slower PV beating rate, larger Ca2+i transients and SR Ca2+ content, smaller late Na+ and NCX currents than AVP (1 μM)-treated PV cardiomyocytes. Western blot experiments showed that AVP (1 μM) treated PV cardiomyocytes had higher expression of NCX and p-CaMKII, and a higher ratio of p-CaMKII/CaMKII.ConclusionsAVP increases PV arrhythmogenesis with dysregulated Ca2+ homeostasis through vasopressin V1 signaling.
Highlights
Arginine vasopressin (AVP), is a nonapeptide produced by the posterior pituitary gland, mainly synthesized and secreted in the hypothalamus
Since arginine vasopressin (AVP) signaling may modulate Ca2+ homeostasis, we suggest that enhanced AVP might contribute to Pulmonary veins (PVs) arrhythmogenesis
Effect of AVP and AVP receptor antagonists on ionic currents of PV cardiomyocytes Figure 2 shows that AVP (1 μM)-treated PV cardiomyocytes had a 58% larger INa-Late than the control cells
Summary
Arginine vasopressin (AVP), is a nonapeptide produced by the posterior pituitary gland, mainly synthesized and secreted in the hypothalamus. IP3 induces calcium (Ca2+) release from the sarcoplasmic reticulum (SR) [10, 11], whereas DAG activates protein kinase C, which opens voltage-gated Ca2+ channels and closes potassium channels [11]. Liberated AVP increases sympathetic outflow to the cardiovascular system and may increase the risk of arrhythmia and sudden death [13]. Earlier studies showed that increased AF occurrence in patients with postoperative vasoplegic shock more frequently experienced new AF with prolonged AVP therapy [14, 15]. Atrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms
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