Angiotensin Ii Hypertension-dependent Decrease In Circadian Rhythms Of Cardiovascular Parameters: Role Of Peroxisome Proliferator Activated Receptor-[alpha]

Decreases in circadian rhythms of cardiovascular parameters, such as day to night changes in mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), systolic (SP) and diastolic pressure (DP) are an index of cardiovascular disease. Peroxisome proliferator activated receptor - alpha (PPAR-α) has been shown to decrease inflammatory markers and hypertension a slow pressor dose of Angiotensin II (Ang II); however, the role of PPAR-α on cardiovascular parameters during the initial stages of Ang II infusion is unknown. We hypothesize that the absence of PPAR-α will cause a reduction in the day to night changes in MAP, HR, PP, SP and DP during the initial stages of a slow pressor dose of Ang II. Male (10 - 12 weeks old) PPAR-αknockout (KO) and wild-type (WT) mice were infused with Ang II (400 ng/kg/min) for three days. Radiotelemetry was used to measure the cardiovascular parameters. The baseline MAP values were: 100 + 10 mmHg (WT) and 108 + 9 mmHg for KO. The baseline HR values were: 530 + 10 bpm (WT) and 526 + 6 bpm (KO). The baseline PPs were 17 + 0.2 mmHg (WT) and 18 + 0.3 mmHg (KO). The baseline SBPs were 108 + 9 mmHg (WT) and 116 + 10 mmHg (KO). The baseline DBPs were 91 + 9 mmHg (WT) and 98 + 10 mmHg (KO). During the first three days of Ang II infusion, the change in day to night MAP was 20 ± 2 mmHg and 10 ± 2 mmHg in Ang II treated WT and KO mice, respectively. Changes in day to night HR were 25 ± 4 bpm and 46 ± 7 bpm for WT and KO mice, respectively. The day to night changes in PP were 8 ± 1 mmHg for WT and 2 ± 2 mmHg for KO mice. The day to night changes in SBPs were 20 ± 2 mmHg and 12 ± 3 mmHg for WT and KO mice, respectively. Changes in day to night DBPs were 18 ± 2 mmHg for WT and 9 ± 2 mmHg for KO mice. TBARS and Interleukin-17 were increased in heart homogenates of KO + Ang II (15 ± 2 μM) and (1.5 ± 0.3 ng/mL) vs WT + Ang II (11 ± 3 μM) and (1.0 ± 0.2 ng/mL). Nitrite/Nitrate was decreased in KO + Ang II (1.0 ± 0.1 nM) vs WT + Ang II (1.5 ± 0.5 nM). In summary, the absence of PPAR-α decreases the day to night changes in MAP, SBP, DBP and PP during the initial three days of a slow pressor dose of Ang II. In the absence of PPAR-α, increases in oxidative stress and inflammation are mechanisms that may contribute to the changes in the cardiovascular parameters and suggest the occurrence of cardiovascular diseases during a slow pressor dose of Ang II-infusion.