Depressed Heart Rate Variability and Arterial Baroreflex in Conscious Transgenic Mice With Overexpression of Cardiac G _sα

Abstract

Recently, we developed a transgenic mouse with cardiac-specific Gsalpha overexpression (TG mouse), which exhibits enhanced postsynaptic beta-adrenergic receptor signaling, ultimately developing a cardiomyopathy. The goal of the present study was to determine whether cardiac Gsalpha overexpression alters autonomic cardiovascular control, which could shed light on the mechanism responsible for the later development of cardiomyopathy. Mean arterial pressure was increased (P<.05) in conscious, chronically instrumented TG mice (123+/-1 mm Hg) compared with age-matched wild-type (WT) control mice (103+/-1 mm Hg). Respiratory frequency was increased (P<.05) in TG mice (269+/-26/min) compared with WT mice (210+/-20/min). By use of telemetric techniques, baseline heart rate (HR) was elevated (P<.05) in conscious, untethered TG mice (696+/-13 bpm) compared with WT mice (568+/-28 bpm). Intrinsic HR, after propranolol and atropine or after ganglionic blockade with hexamethonium, was not different between TG and WT mice. Both the normal minute-to-minute and circadian variations of HR observed in WT mice were markedly blunted in TG mice. HR variability was assessed by the time-domain and frequency-domain methods. At baseline, time-domain analysis indices were reduced (P<.05) in TG mice compared with WT mice. Although the low frequency (LF) component was higher (P<.05) than the high frequency (HF) component in WT mice, the LF component was less (P<.05) than the HF component in TG mice. In addition, arterial baroreflex regulation of HR was markedly blunted in TG mice in response to both nitroglycerin-induced hypotension and phenylephrine-induced hypertension. The reduced LF/HF ratio in TG mice was surprising in view of enhanced beta-adrenergic signaling and may be due to reduced neural tone secondary to the elevated arterial pressure or alterations in arterial baroreflex control. Dobutamine infusion in WT mice also resulted in depressed HR variability. The combination of elevated baseline HR, arterial pressure, and respiratory frequency suggests that enhanced beta-adrenergic signaling in TG mice results in reduced HR variability, in terms of both minute-to-minute variability and the lack of circadian variations in HR. The lack of normal HR variability in general and the failure of HR to decline, even during sleep, may actually be critical mechanisms contributing to the ultimate development of cardiomyopathy in these animals.

Spectral analysis of heart rate variability in elderly non-dipper hypertensive patients

“…All these data suggest that in the earlier stages, arterial hypertension may be accompanied by sympathetic overactivity, decreased parasympathetic tone, and impaired activity of baroceptors leading to blunted HRV. [36][37][38][39][40][41] It can also be considered as a pathologic condition related, in the elderly, to a decrease of autonomic nervous system activity clearer in non-dipper subjects. A similar pattern was recently reported by Abate et al 42 in elderly hypertensive subjects, confirming that non-dipper hypertensives present a significant impairment in the autonomic nervous drive, characterised by a decreased parasympathetic tone.…”

Exercise training changes autonomic cardiovascular balance in mice

“…Vagal and sympathetic function and IHR were measured by determining the response to methylatropine (1 mg/kg iv) and propranolol (1 mg/kg iv) with a maximal injection volume of 40 l in a 2-day protocol (35). Because the HR responses to methylatropine and propranolol reach their peak in 3 min, this time interval was used to quantify the drug-induced HR changes.…”

Effects of anesthesia on conventional and speckle tracking echocardiographic parameters in a mouse model of pressure overload

“…There were a number of limitations to the present study: Firstly, conscious mice were not included as a control, as the elevation of sympathetic tone during conscious measurement could not be fully eliminated, despite the mice undergoing training a few days prior to the experiment (27). In addition, the images used for strain analysis must be of high resolution, with clear visualization of the endocardium and epicardium borders.…”