Circadian Rhythm of Pulse Pressure are decreased in Peroxisome Proliferator Activated Receptor‐α Knockout Mice during Angiotensin II Hypertension

Circadian rhythm of pulse pressure is considered an index of cardiovascular disease. An elevated pulse pressure is commonly associated with increased stiffness of the aorta due to high blood pressure. Activation of PPAR‐a has been shown to decrease hypertension; however, the role of PPAR‐a on pulse pressure during Angiotensin II hypertension is not well understood. We tested the hypothesis that the absence of PPAR‐α would decrease changes in the circadian rhythm of pulse pressure during Angiotension II (Ang II) hypertension. Male (10 – 12 weeks old) PPAR‐alpha knockout (KO) mice and their wild‐type (WT) control were infused with Ang II (400 ng/kg/min) for 12 days. Day and night systolic, diastolic, pulse and mean arterial pressures, along with heart rate and locomotor activity was collected 19‐hrs/day. The average change in day to night pulse pressure was 1 ± .05 and 3 ± .1 mmHg in Ang II treated KO and WT mice, respectively. No differences in day to night heart rate were observed between KO (30 ± 3 bpm) and WT (30 ± 5 bpm). Day to night changes in locomotor activity, systolic, diastolic and mean arterial pressures were similar between both groups. TBARS were increased in KO + Ang II (15 ± 2 mM) vs WT + Ang II (11 ± 3 mM). Nitrite/Nitrate was decreased in KO + Ang II (1.0 ± 0.1 nM) vs WT + Ang II (1.5 ± 0.5 nM). Interleukin 17 was increased in KO + Ang II (1.5 ± 0.3 ng/mL) vs WT + Ang II (1.0 ± 0.2 ng/mL). Our results suggest that PPAR‐alpha activation increases the circadian rhythm of pulse pressure by decreasing oxidative stress, and IL‐17 concentrations while increasing nitrite/nitrate concentrations during Ang II hypertension. Support or Funding Information 5K01HL092593‐05