Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice

• Verfasst von: Dewenter, Matthias [VerfasserIn]
• Verfasst von: Pan, Jianyuan [VerfasserIn]
• Verfasst von: Knödler, Laura-Louise [VerfasserIn]
• Verfasst von: Tzschöckel, Niklas [VerfasserIn]
• Verfasst von: Henrich, Julian [VerfasserIn]
• Verfasst von: Cordero, Julio [VerfasserIn]
• Verfasst von: Dobreva, Gergana [VerfasserIn]
• Verfasst von: Lutz, Susanne [VerfasserIn]
• Verfasst von: Backs, Johannes [VerfasserIn]
• Verfasst von: Wieland, Thomas [VerfasserIn]
• Verfasst von: Vettel, Christiane [VerfasserIn]
• Titel: Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice
• Titelzusatz: critical contribution of alpha1-adrenoceptors to early cardiac stress responses : original contribution
• Verf.angabe: Matthias Dewenter, Jianyuan Pan, Laura Knödler, Niklas Tzschöckel, Julian Henrich, Julio Cordero, Gergana Dobreva, Susanne Lutz, Johannes Backs, Thomas Wieland, Christiane Vettel
• E-Jahr: 2022
• Jahr: 14 March 2022
• Umfang: 23 S.
• Fussnoten: Im Titelzusatz ist die "1" tiefgestellt ; Gesehen am 30.05.2023
• Titel Quelle: Enthalten in: Basic research in cardiology
• Ort Quelle: [Darmstadt u.a.] : Steinkopff, 1937
• Jahr Quelle: 2022
• Band/Heft Quelle: 117(2022) vom: März, Artikel-ID 15, Seite 1-23
• ISSN Quelle: 1435-1803
• DOI: doi:10.1007/s00395-022-00920-z
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cardiac fibroblast activation
• Sach-SW: Isoprenaline
• Sach-SW: Neurohumoral models of cardiac remodeling
• Sach-SW: Phenylephrine
• Sach-SW: α1- and β-adrenoceptors
• Sach-SW: α1-adrenergic inotropy
• K10plus-PPN: 1846830761
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Hyperactivity of the sympathetic nervous system is a major driver of cardiac remodeling, exerting its effects through both α-, and β-adrenoceptors (α-, β-ARs). As the relative contribution of subtype α1-AR to cardiac stress responses remains poorly investigated, we subjected mice to either subcutaneous perfusion with the β-AR agonist isoprenaline (ISO, 30 mg/kg × day) or to a combination of ISO and the stable α1-AR agonist phenylephrine (ISO/PE, 30 mg/kg × day each). Telemetry analysis revealed similar hemodynamic responses under both ISO and ISO/PE treatment i.e., permanently increased heart rates and only transient decreases in mean blood pressure during the first 24 h. Echocardiography and single cell analysis after 1 week of exposure showed that ISO/PE-, but not ISO-treated animals established α1-AR-mediated inotropic responsiveness to acute adrenergic stimulation. Morphologically, additional PE perfusion limited concentric cardiomyocyte growth and enhanced cardiac collagen deposition during 7 days of treatment. Time-course analysis demonstrated a diverging development in transcriptional patterns at day 4 of treatment i.e., increased expression of selected marker genes Xirp2, Nppa, Tgfb1, Col1a1, Postn under chronic ISO/PE treatment which was either less pronounced or absent in the ISO group. Transcriptome analyses at day 4 via RNA sequencing demonstrated that additional PE treatment caused a marked upregulation of genes allocated to extracellular matrix and fiber organization along with a more pronounced downregulation of genes involved in metabolic processes, muscle adaptation and cardiac electrophysiology. Consistently, transcriptome changes under ISO/PE challenge more effectively recapitulated early transcriptional alterations in pressure overload-induced experimental heart failure and in human hypertrophic cardiomyopathy.