Disruption of cardiovascular circadian rhythms in mice post myocardial infarction: relationship with central angiotensin II receptor expression

Abstract

Angiotensin II (Ang II) is well known to participate in the abnormal autonomic cardiovascular control that occurs during the development of chronic heart failure (CHF). Disrupted cardiovascular circadian rhythm in CHF is also well accepted; however, the mechanisms underlying and the role of central Ang II type 1 receptors (AT1R) and oxidative stress in mediating such changes are not clear. In a post myocardial infarction (MI) CHF mouse model we investigated the circadian rhythm for mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity (BRS) following MI. The cardiovascular parameters represent the middle 6‐h averages during daytime (6:00–18:00) and nighttime (18:00–6:00). HR increased with the severity of CHF reaching its maximum by 12 weeks post‐MI; loss of circadian HR and BRS rhythms were observed as early as 4 weeks post‐MI in conjunction with a significant blunting of the BRS and an upregulation in the AT1R and gp91phox proteins in the brainstem. Loss of MAP circadian rhythm was observed 8 weeks post‐MI. Circadian AT1R expression was demonstrated in sham animals but was lost 8 weeks following MI. Losartan reduced AT1R expression in daytime (1.18 ± 0.1 vs. 0.85 ± 0.1; P < 0.05) with a trend toward a reduction in the AT1R mRNA expression in the nighttime (1.2 ± 0.1 vs. 1.0 ± 0.1; P > 0.05) but failed to restore circadian variability. The disruption of circadian rhythm for HR, MAP and BRS along with the upregulation of AT1 and gp91phox suggests a possible role for central oxidative stress as a mediator of circadian cardiovascular parameters in the post‐MI state.

Chronic Heart Failure Abolishes Circadian Rhythms in Resting and Chemoreflex Breathing

“…Light/dark variations in respiration and arterial pressure appear to be abolished in CHF with reduced ejection fraction. Our study corroborates previous work on blood pressure rhythms in human heart failure patients (Komori et al 2016) and mice with myocardial infarctions (Mousa et al 2014). The current study expands previous findings in showing that CHF also eliminates respiratory circadian rhythms.…”

Plastics and cardiovascular health: phthalates may disrupt heart rate variability and cardiovascular reactivity

“…Each hour, HR and BP signals were sampled and analyzed [120-s continuous segment (80)], resulting in 12 data points per daytime (12 h) and nighttime (12 h). Daytime and nighttime data were averaged across the 12-h timeframe and displayed with two representative data points per week of the 6-wk study, similar to other analysis methods for long-term telemetry recordings (58,80).…”

“…Emerging epidemiological studies have shown correlations between phthalate exposure and human health concerns, including neurological disorders and cardiovascular disease (14,22,32,58,76,78). The latter includes an association between phthalate plasticizer exposure and increased systolic blood pressure (SBP) in adolescents (83,84) and an increased coronary risk in elderly populations (46,60).…”

Differential Regulation of BMAL1, CLOCK, and Endothelial Signaling in the Aortic Arch and Ligated Common Carotid Artery

“…Blood pressure [28–30], vascular remodeling [8, 10, 31–33], atherosclerosis [13], cardiac injury [34–37], and coagulation [38] are all influenced by circadian clock genes. Thus, this molecular regulator of 24-h rhythmicity controls not only daily and acute pathophysiology, such as blood pressure and thrombosis, but also chronic responses.…”