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Oral propranolol reduces cardiac sympathetic activity in mice
Victor Chu, Jose M. Otero, Orlando Lopez, Adam Rosenthal, Ivo Amende,
and Thomas G. Hampton; Mouse Specifics, Inc., Boston, MA. USA.
Web published: Sept. 1, 2001
Abstract
Propranolol is an effective treatment for heart diseases and is a useful adjunct to neuroleptic therapy for schizophrenia. The increase in the number of mouse models for examining the autonomic nervous system compelled us to screen the effect of propranolol on the electrocardiogram (ECG) in mice. Accordingly we non-invasively recorded ECGs in adult male FVB mice orally administered propranolol. We found that heart rate decreased ~10% in propranolol-treated mice compared to untreated mice (P<0.05). Heart rate variability increased significantly, consistent with ß-adrenergic modulation of the sympathetic nervous system.
Methods
Figure 1.(*P<0.05)
Figure 2.(*P<0.05)
Adult male FVB mice (n=14) were obtained from The Jackson Laboratory. The AnonyMOUSETM ECG screening system was used to record ECGs.1 Neither anesthetic nor surgery was required. After baseline recordings were performed, water bottles for 7 mice were replaced with bottles containing 0.5 g/L propranolol.2 Recordings were repeated on the subsequent 4 days. Data were acquired at 2kHz for at least 2 seconds to provide equivalent continuous recordings of 20 to 30 beats. e-MOUSETM was used to interpret the signals. Time domain indices of heart rate (HR) variability (var), e.g., HR var and the coefficient of variance (CV%), were calculated as described previously.3
Results
Effects of Propranolol on Day 2.
Baseline (n=14)
Propranolol (n=7)
HR (bpm)
775 ± 1
702 ± 28*
PR (ms)
23.9 ± 0.7
26.0 ± 1.4
QRS (ms)
7.9 ± 0.1
8.4 ± 0.3*
HR var (bpm)
9 ± 1
15 ± 3*
CV (%)
1.2 ± 0.1
2.2 ± 0.6*
*P < 0.05 via Student's 2-tail unpaired
t-test.
Discussion
Propranolol is a non-selective competitive antagonist of ß-adrenergic receptors that has been shown to reduce infarct size after coronary occlusion4, improve survival after acute myocardial infarction5, improve prognosis in heart failure6, blunt oxidative stress7, and benefit schizophrenic patients8. We found that in adult male FVB mice, oral administration of propranolol resulted in a significant decrease (~10%) in heart rate, similar to what others have reported in 129Sv7 and C57BL/69,10 mice following intraperitoneal injection of propranolol. Importantly, our studies were conducted in conscious mice without implanted instrumentation, and therefore free of the confounding effects of anesthesia or surgery. Oral propranolol resulted in significant electrocardiographic changes within 1 day. Our protocol provides a rapid means for non-invasively altering and monitoring sympathetic nervous activity in mice. Our observations are consistent with the notion that in mice, the sympathetic nervous system may play a more prominent role in the control of resting heart rate.3,10,11
References
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