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Activation of SUR2B/Kir6.1 subtype of adenosine triphosphate-sensitive potassium channel improves pressure overload-induced cardiac remodeling via protecting endothelial function.
J Cardiovasc Pharmacol. 2010 Oct; 56(4):345-53.JC

Abstract

We sought to explore new strategies targeting SUR2B/Kir6.1, a subtype of adenosine triphosphate (ATP)-sensitive potassium channels (KATP), against pressure overload-induced heart failure. The effects of natakalim, a SUR2B/Kir6.1 selective channel opener, on progression of cardiac remodeling were investigated. Pressure overload-induced heart failure was induced in Wistar rats by abdominal aortic banding. The effects of natakalim (1, 3, and 9 mg·kg⁻¹·d⁻¹ for 10 weeks) on myocardial hypertrophy and heart failure, cardiac histology, vasoactive compounds, and gene expression were assessed. Ten weeks after the onset of pressure overload, natakalim treatment potently inhibited cardiac hypertrophy and prevented heart failure. Natakalim remarkably inhibited the changes of left ventricular hemodynamic parameters and reversed the increase of heart mass index, left ventricular weight index, and lung weight index. Histological examination demonstrated that there was no significant hypertrophy or fibrosis in pressure-overloaded hearts of natakalim-treated rats. Ultrastructural examination of hearts revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in rats from the natakalim group. The content of serum nitric oxide and plasma prostacyclin was increased, whereas that of plasma endothelin-1 and cardiac tissue hydroxyproline and atrial and B-type natriuretic peptide messenger RNA was downregulated in natakalim-treated rats. Natakalim at 0.01-100 µM had no effects on isolated working hearts derived from Wistar rats; however, natakalim had endothelium-dependent vasodilatory effects on the isolated tail artery helical strips precontracted with norepinephrine. These results indicate that natakalim reduces heart failure caused by pressure overloading by activating the SUR2B/Kir6.1 KATP channel subtype and protecting against endothelial dysfunction.

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Authors+Show Affiliations

Tang Y
Department of Cardiovascular Pharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Long CL
No affiliation info available
Wang RH
No affiliation info available
Cui W
No affiliation info available
Wang H
No affiliation info available

MeSH

ATP-Binding Cassette TransportersAllyl CompoundsAnimalsBlood PressureCardiomegalyCardiovascular AgentsDose-Response Relationship, DrugEndothelial CellsEndothelin-1Endothelium, VascularEpoprostenolHeart FailureHypertensionIn Vitro TechniquesKATP ChannelsMaleMyocardiumNitric OxidePotassium Channels, Inwardly RectifyingPropylaminesRatsRats, WistarReceptors, DrugSulfonylurea ReceptorsTailVasodilator AgentsVentricular Remodeling

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20505525

Citation

Tang, Yuan, et al. "Activation of SUR2B/Kir6.1 Subtype of Adenosine Triphosphate-sensitive Potassium Channel Improves Pressure Overload-induced Cardiac Remodeling Via Protecting Endothelial Function." Journal of Cardiovascular Pharmacology, vol. 56, no. 4, 2010, pp. 345-53.
Tang Y, Long CL, Wang RH, et al. Activation of SUR2B/Kir6.1 subtype of adenosine triphosphate-sensitive potassium channel improves pressure overload-induced cardiac remodeling via protecting endothelial function. J Cardiovasc Pharmacol. 2010;56(4):345-53.
Tang, Y., Long, C. L., Wang, R. H., Cui, W., & Wang, H. (2010). Activation of SUR2B/Kir6.1 subtype of adenosine triphosphate-sensitive potassium channel improves pressure overload-induced cardiac remodeling via protecting endothelial function. Journal of Cardiovascular Pharmacology, 56(4), 345-53. https://doi.org/10.1097/FJC.0b013e3181e6c7b8
Tang Y, et al. Activation of SUR2B/Kir6.1 Subtype of Adenosine Triphosphate-sensitive Potassium Channel Improves Pressure Overload-induced Cardiac Remodeling Via Protecting Endothelial Function. J Cardiovasc Pharmacol. 2010;56(4):345-53. PubMed PMID: 20505525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of SUR2B/Kir6.1 subtype of adenosine triphosphate-sensitive potassium channel improves pressure overload-induced cardiac remodeling via protecting endothelial function. AU - Tang,Yuan, AU - Long,Chao-Liang, AU - Wang,Ru-Huan, AU - Cui,Wenyu, AU - Wang,Hai, PY - 2010/5/28/entrez PY - 2010/5/28/pubmed PY - 2011/3/11/medline SP - 345 EP - 53 JF - Journal of cardiovascular pharmacology JO - J Cardiovasc Pharmacol VL - 56 IS - 4 N2 - We sought to explore new strategies targeting SUR2B/Kir6.1, a subtype of adenosine triphosphate (ATP)-sensitive potassium channels (KATP), against pressure overload-induced heart failure. The effects of natakalim, a SUR2B/Kir6.1 selective channel opener, on progression of cardiac remodeling were investigated. Pressure overload-induced heart failure was induced in Wistar rats by abdominal aortic banding. The effects of natakalim (1, 3, and 9 mg·kg⁻¹·d⁻¹ for 10 weeks) on myocardial hypertrophy and heart failure, cardiac histology, vasoactive compounds, and gene expression were assessed. Ten weeks after the onset of pressure overload, natakalim treatment potently inhibited cardiac hypertrophy and prevented heart failure. Natakalim remarkably inhibited the changes of left ventricular hemodynamic parameters and reversed the increase of heart mass index, left ventricular weight index, and lung weight index. Histological examination demonstrated that there was no significant hypertrophy or fibrosis in pressure-overloaded hearts of natakalim-treated rats. Ultrastructural examination of hearts revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in rats from the natakalim group. The content of serum nitric oxide and plasma prostacyclin was increased, whereas that of plasma endothelin-1 and cardiac tissue hydroxyproline and atrial and B-type natriuretic peptide messenger RNA was downregulated in natakalim-treated rats. Natakalim at 0.01-100 µM had no effects on isolated working hearts derived from Wistar rats; however, natakalim had endothelium-dependent vasodilatory effects on the isolated tail artery helical strips precontracted with norepinephrine. These results indicate that natakalim reduces heart failure caused by pressure overloading by activating the SUR2B/Kir6.1 KATP channel subtype and protecting against endothelial dysfunction. SN - 1533-4023 UR - https://www.unboundmedicine.com/medline/citation/20505525/Activation_of_SUR2B/Kir6_1_subtype_of_adenosine_triphosphate_sensitive_potassium_channel_improves_pressure_overload_induced_cardiac_remodeling_via_protecting_endothelial_function_ L2 - https://doi.org/10.1097/FJC.0b013e3181e6c7b8 DB - PRIME DP - Unbound Medicine ER -