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-1 and -2 adrenergic receptor subtypes on heart rate variability
1 Pediatrics, Stanford University, Stanford, CA, USA
2 Pediatrics, Veterans General Hospital, Kaohsiung, Taiwan
3 Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA
* To whom correspondence should be addressed. E-mail: danb{at}stanford.edu.
-adrenergic receptors (-ARs) play a major role in regulating heart rate and contractility in the intact cardiovascular system. Three subtypes (1, 2, and 3) are expressed in heart tissue and the role of each subtype in regulating cardiac function has previously been determined using both pharmacologic and gene targeting approaches. However, previous studies have only examined the role of -ARs in the macro-level regulation of heart rate. We employed three knockout mouse lines, 1-KO, 2-KO, and 1/2 double knockout (DL-KO), to examine the role that -AR subtypes play in heart rate variability (HRV) and in the sympathetic and parasympathetic inputs into heart rate control. Fast Fourier Transformation (FFT) in frequency domain methods of electrocardiogram (ECG) spectral analysis was used to resolve HRV into high and low frequency (HF and LF) powers. Resting heart rate was decreased in 1-KO (488±27) and DL-KO (495±12) mice compared with WT (638±30) or 2-KO (656±51) (p<0.0005). Mice lacking 1-ARs (1-KO and DL-KO) had increased HRV (as illustrated by the standard deviation of normal R-R intervals or SDNN), and increased normalized (n) HF powers and increased nLF powers compared with mice with intact 1-ARs (WT and 2-KO). These results demonstrate the differential role of -AR subtypes in regulating autonomic signaling.
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