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Various subtypes of phosphodiesterase inhibitors differentially regulate pulmonary vein and sinoatrial node electrical activities

  • Authors:
    • Yung‑Kuo Lin
    • Chen‑Chuan Cheng
    • Jen‑Hung Huang
    • Yi‑Ann Chen
    • Yen‑Yu Lu
    • Yao‑Chang Chen
    • Shih‑Ann Chen
    • Yi‑Jen Chen

  • View Affiliations

  • Published online on: February 7, 2020     https://doi.org/10.3892/etm.2020.8495
  • Pages: 2773-2782
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Abstract

Phosphodiesterase (PDE)3‑5 are expressed in cardiac tissue and play critical roles in the pathogenesis of heart failure and atrial fibrillation. PDE inhibitors are widely used in the clinic, but their effects on the electrical activity of the heart are not well understood. The aim of the present study was to examine the effects of various PDE inhibitors on spontaneous cardiac activity and compare those effects between sinoatrial nodes (SANs) and pulmonary veins (PVs). Conventional microelectrodes were used to record action potentials in isolated rabbit SAN and PV tissue preparations, before and after administration of different concentrations (0.1, 1 and 10 µM) of milrinone (PDE3 inhibitor), rolipram (PDE4 inhibitor) and sildenafil (PDE5 inhibitor), with or without the application of isoproterenol (cAMP and PKA activator), KT5823 (PKG inhibitor) or H89 (PKA inhibitor). Milrinone (1 and 10 µM) increased the spontaneous activity in PVs by 10.6±4.9 and 16.7±5.3% and in SANs by 9.3±4.3 and 20.7±4.6%, respectively. In addition, milrinone (1 and 10 µM) induced the occurrence of triggered activity (0/8 vs. 5/8; P<0.005) in PVs. Rolipram increased PV spontaneous activity by 7.5±1.3‑9.5±4.0%, although this was not significant, and did not alter SAN spontaneous activity. Sildenafil reduced spontaneous activity in PVs to a greater extent than that seen in SANs. Both KT5823 and H89 suppressed milrinone‑increased PV spontaneous activity. In the presence of isoproterenol, milrinone did not alter isoproterenol‑induced PV arrhythmogenesis, suggesting that the effects of PDE3 are mediated by the protein kinase G and protein kinase A signaling pathways. In conclusion, inhibitors of different PDE subtypes exert diverse electrophysiological effects on PV and SAN activities.
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April-2020
Volume 19 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Lin YK, Cheng CC, Huang JH, Chen YA, Lu YY, Chen YC, Chen SA and Chen YJ: Various subtypes of phosphodiesterase inhibitors differentially regulate pulmonary vein and sinoatrial node electrical activities. Exp Ther Med 19: 2773-2782, 2020
APA
Lin, Y., Cheng, C., Huang, J., Chen, Y., Lu, Y., Chen, Y. ... Chen, Y. (2020). Various subtypes of phosphodiesterase inhibitors differentially regulate pulmonary vein and sinoatrial node electrical activities. Experimental and Therapeutic Medicine, 19, 2773-2782. https://doi.org/10.3892/etm.2020.8495
MLA
Lin, Y., Cheng, C., Huang, J., Chen, Y., Lu, Y., Chen, Y., Chen, S., Chen, Y."Various subtypes of phosphodiesterase inhibitors differentially regulate pulmonary vein and sinoatrial node electrical activities". Experimental and Therapeutic Medicine 19.4 (2020): 2773-2782.
Chicago
Lin, Y., Cheng, C., Huang, J., Chen, Y., Lu, Y., Chen, Y., Chen, S., Chen, Y."Various subtypes of phosphodiesterase inhibitors differentially regulate pulmonary vein and sinoatrial node electrical activities". Experimental and Therapeutic Medicine 19, no. 4 (2020): 2773-2782. https://doi.org/10.3892/etm.2020.8495