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The hypertensive response to L‐NAME and Angiotensin II in circadian clock mutant mice
Author(s) -
Pati Paramita,
Anea Ciprian B.,
Rudic R. Daniel
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.1084.10
Subject(s) - per2 , circadian rhythm , blood pressure , medicine , endocrinology , circadian clock , heart rate , angiotensin ii , clock
In order to determine whether mutation of the circadian clock affects the response to experimental hypertension, we undertook studies to examine response to pressor agents in mice with targeted disruption of Bmal1 (Bmal1‐KO mice) and Period2 (Per2‐KO mice), using radiotelemetry to monitor blood pressure, activity, and heart rate. Using L‐nitro arginine methyl ester (L‐NAME) and additional studies with Angiotensin II, hypertension was induced. In Per2‐KO mice, we also assessed the influence of standard 12:12‐h light‐dark schedule (LD) versus conditions of constant darkness (DD) on cardiovascular rhythms and activity +/−L‐NAME treatment. We found that Bmal1‐KO mice display a blunted hypertensive response to L‐NAME. In contrast, the elevation of blood pressure induced by L‐NAME did not differ between Per2‐KO and WT. Interestingly, DD conditions induced a phase advance in blood pressure and heart rate in Per2 KO mice, and a return to LD from DD allowed a restoration of the original phase yet blood pressure was increased. Despite the phase advance in blood pressure and heart rate, circadian rhythm of blood pressure was intact, while DD induced complete ablation of circadian locomotor activity in Per2‐KO, suggesting that locomotor rhythm and blood pressure rhythms may not be completely co‐dependent. These studies may reveal an important influence of the circadian clock in conditioning hypertension.