Experimental heart failure in rats: effects on cardiovascular circadian rhythms and on myocardial β-adrenergic signaling
Objectives: Patients with chronic heart failure frequently show blunted circadian blood pressure profiles. The mechanisms involved in the loss of physiological day-night variation are still unclear, but a continuously active sympathetic nervous system could play a role. The present study evaluated l...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
01 August 2000
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| In: |
Cardiovascular research
Year: 2000, Jahrgang: 47, Heft: 2, Pages: 350-358 |
| ISSN: | 1755-3245 |
| DOI: | 10.1016/S0008-6363(00)00099-7 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S0008-6363(00)00099-7
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| Verfasserangaben: | Klaus Witte, Kai Hu, Johanna Swiatek, Claudia Müssig, Georg Ertl, Björn Lemmer |
| Zusammenfassung: | Objectives: Patients with chronic heart failure frequently show blunted circadian blood pressure profiles. The mechanisms involved in the loss of physiological day-night variation are still unclear, but a continuously active sympathetic nervous system could play a role. The present study evaluated long-term consequences of rat heart failure on cardiovascular circadian patterns in vivo, and on density and function of cardiac β-adrenoceptor subtypes in vitro, as a marker of cardiac adrenergic drive. Methods: Heart failure in rats was induced by coronary artery ligation leading to infarct sizes of >30% of left ventricular circumference. Blood pressure and heart rate were monitored for 10 weeks after infarction using radiotelemetry. Density and function of cardiac β1 and β2-adrenoceptors were measured by radioligand binding and adenylyl cyclase stimulation. Results: During the activity period at night blood pressure and heart rate were lower in rats with heart failure than in sham controls, leading to reduced night-day variation in the heart failure group. Depression of circadian rhythmicity in blood pressure was found over the whole study period, while that in heart rate occurred with a lag-time of several weeks. In failing left ventricles β-adrenoceptors showed reduced high affinity agonist binding, a shift in the β1:β2 ratio towards the β2-subtype, and decreased β1-adrenergic stimulation of adenylyl cyclase. In right ventricles no differences were found between failing and control rats. The blunted nocturnal increase in blood pressure and heart rate as well as β1-adrenergic desensitization were correlated with the severity of left ventricular dysfunction. Conclusions: Heart failure in rats leads to disturbed circadian patterns in blood pressure and heart rate, and to desensitization of cardiac β1-adrenoceptors, indicating chronic sympathetic overactivity. |
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| Beschreibung: | Gesehen am 14.04.2022 |
| Beschreibung: | Online Resource |
| ISSN: | 1755-3245 |
| DOI: | 10.1016/S0008-6363(00)00099-7 |