Effect of targeted deletions of beta1- and beta2-adrenergic-receptor subtypes on heart rate variability

Autor: Anne M. Dubin, Phillip M. Ecker, Chu-Chuan Lin, Jennifer Powers, Brian K. Kobilka, Daniel Bernstein
Rok vydání: 2005
Předmět:
Zdroj: American journal of physiology. Heart and circulatory physiology. 290(1)
ISSN: 0363-6135
Popis: β-Adrenergic receptors (β-ARs) play a major role in regulating heart rate (HR) and contractility in the intact cardiovascular system. Three subtypes (β1, β2, and β3) are expressed in heart tissue, and the role of each subtype in regulating cardiac function has previously been determined by using both pharmacological and gene-targeting approaches. However, previous studies have only examined the role of β-ARs in the macrolevel regulation of HR. We employed three knockout (KO) mouse lines, β1-KO, β2-KO, and β1/β2 double KO (DL-KO), to examine the role that β-AR subtypes play in HR variability (HRV) and in the sympathetic and parasympathetic inputs into HR control. Fast Fourier transformation (FFT) in frequency domain methods of ECG spectral analysis was used to resolve HRV into high- and low-frequency (HF and LF) powers. Resting HR (in beats/min) was decreased in β1-KO [488 (SD 27)] and DL-KO [495 (SD 12)] mice compared with wild-type [WT; 638 (SD 30)] or β2-KO [656 (SD 51)] ( P < 0.0005) mice. Mice lacking β1-ARs (β1-KO and DL-KO) had increased HRV (as illustrated by the standard deviation of normal R-R intervals) and increased normalized HF and LF powers compared with mice with intact β1-ARs (WT and β2-KO). These results demonstrate the differential role of β-AR subtypes in regulating autonomic signaling.
Databáze: OpenAIRE