Experimental heart failure in rats: Effects on cardiovascular circadian rhythms and on myocardial β-adrenergic signaling

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Abstract

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 β 1 and β 2 -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 β 1 :β 2 ratio towards the β 2 -subtype, and decreased β 1 -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 β 1 - 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 β 1 -adrenoceptors, indicating chronic sympathetic overactivity. (C) 2000 Elsevier Science B.V.

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APA

Witte, K., Hu, K., Swiatek, J., Müssig, C., Ertl, G., & Lemmer, B. (2000). Experimental heart failure in rats: Effects on cardiovascular circadian rhythms and on myocardial β-adrenergic signaling. Cardiovascular Research, 47(2), 350–358. https://doi.org/10.1016/S0008-6363(00)00099-7

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