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 gp91(phox) 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 gp91(phox) suggests a possible role for central oxidative stress as a mediator of circadian cardiovascular parameters in the post-MI state.