Premium
Alpha 1 Adrenergic‐mediated Vasoconstriction is Attenuated in Peroxisome Proliferator Activated Receptor‐ α knockout mice during Angiotensin II Hypertension
Author(s) -
Wilson Justin L.,
Duan Rong,
Lee Dexter L.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1027.19
Subject(s) - medicine , endocrinology , angiotensin ii , blood pressure , phenylephrine , peroxisome proliferator activated receptor , vasoconstriction , renin–angiotensin system , receptor , mean arterial pressure , heart rate , chemistry
Peroxisome proliferator activated receptor‐α (PPAR‐α) has emerged as an important player in the pathogenesis of the metabolic syndrome. PPAR‐α also modulates the renin‐angiotensin‐aldosterone system and has anti‐inflammatory properties. Therefore, PPAR–α is important for attenuating hypertension, inflammatory responses, and metabolic derangements associated with obesity. This study determined the role of alpha 1 ‐ adrenergic stimulation by phenylephrine (PE) during Angiotensin II hypertension with the deletion of PPAR‐α. Six to eight week old male PPAR‐α KO mice and their wild‐type controls were infused with Angiotensin II (400 ng/kg/min) (Ang II) (s.c.) for 14 days. On day 12 of Ang II hypertension, mice were given bolus injections (i.v.) of PE (10, 60, 300 μg/kg). Baseline mean arterial pressure and heart rate were not significantly different between PPAR‐α KO (94 ± 5 mmHg, 451 ± 12 bpm) and WT (97 ± 6 mmHg, 461 ± 23 bpm). PE (60 μg/kg) caused a significant increase in the change of systolic blood pressure in PPAR‐α KO (33 ± 3 mmHg) compared to WT (23 ± 4 mmHg) mice. The change in pulse pressure to PE (60 μg/kg) was also increased in PPAR‐α KO (17 ± 3 mmHg) when compared to WT (10 ± 3 mmHg). PPAR‐α KO had a greater decrease in heart rate during PE (60 μg/kg) than WT, 70 ± 5 bpm and 60 ± 3 bpm, respectively. Our data indicates that PPAR‐α KO mice have a greater alpha 1 ‐ adrenergic mediated vasoconstriction and reflex‐mediated fall in heart rate during Ang II hypertension. Our results may suggest that the presence of the PPAR‐α receptor attenuates alpha 1 ‐ adrenergic mediated vasoconstriction during hypertension and may modulate the pathogenesis associated with metabolic syndrome.