Article,

Circadian and short-term regulation of blood pressure and heart rate in transgenic mice with cardiac overexpression of the beta1-adrenoceptor

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Chronobiol Int, 21 (2): 205-16 (March 2004)Witte, Klaus Engelhardt, Stefan Janssen, Ben J A Lohse, Martin Lemmer, Bjorn United States Chronobiology international Chronobiol Int. 2004 Mar;21(2):205-16..

Abstract

Congestive heart failure is associated with a loss of circadian and short-term variability in blood pressure and heart rate. In order to assess the contribution of elevated cardiac sympathetic activity to the disturbed cardiovascular regulation, we monitored blood pressure and heart rate in mice with cardiac overexpression of the beta1-adrenoceptor prior to the development of overt heart failure. Telemetry transmitters for continuous monitoring of blood pressure and heart rate were implanted in 8 to 9-week-old wildtype and transgenic mice, derived from crosses of heterozygous transgenic (line beta1TG4) and wildtype mice. Cardiovascular circadian patterns were analyzed under baseline conditions and during treatment with propranolol (500mg/L in drinking water). Short-term variability was assessed by spectral analysis of beat-to-beat data sampled for 30min at four circadian times. Transgenic beta1TG4 mice showed an increase in 24h heart rate, while blood pressure was not different from wildtype controls. Circadian patterns in blood pressure and heart were preserved in beta1TG4 mice. Addition of propranolol to the animals' drinking water led to a reduction in heart rate and its 24 h variation in both strains of mice. Short-term variability in blood pressure was not different between wildtype and beta1TG4 mice, but heart rate variability in the transgenic animals showed a rightward shift of the high-frequency component in the nocturnal activity period, suggesting an increase in respiratory frequency. In conclusion, the present study shows that both the circadian and the short-term regulation of blood pressure and heart rate are largely preserved in young, nonfailing beta1-transgenic mice. This finding suggests that the loss of blood pressure and heart rate variability observed in human congestive heart failure cannot be attributed solely to sympathetic overactivity but reflects the loss of adrenergic responsiveness to changes in the activity of the autonomic nervous system.

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