Heart Rate Variability and Baroreflex Function in AT2 Receptor-Disrupted Mice

Abstract

We adapted telemetry and sequence analysis employed in humans to mice and measured heart rate variability and the spontaneous baroreflex sensitivity in angiotensin II type 2 (AT2) receptor–deleted (AT2 −/−) and wild-type (AT2 +/+) mice with either deoxycorticosterone acetate (DOCA)-salt hypertension or N&ohgr;-nitro-l-arginine methylester hydrochloride (L-NAME) hypertension. Mean arterial pressure leveled during the day at 101±1 mm Hg and during the night at 109±1 mm Hg in AT2 receptor–deleted mice, compared with 98±2 mm Hg (day) and 104±2 mm Hg (night) in wild-type mice. Mean arterial pressure increased in AT2 receptor–deleted mice with L-NAME to 114±1 mm Hg (day) and 121±1 mm Hg (night), compared with 105±2 mm Hg (day) and 111±2 mm Hg (night), respectively. DOCA-salt also increased day and night blood pressures in AT2 receptor–deleted mice to a greater degree than in wild-type mice. Heart rate variability in the time and frequency domain was not different between AT2 receptor–deleted mice and AT2 receptor–deleted mice at baseline. Systolic blood pressure variability in the low frequency band was lower in AT2 receptor–deleted mice (0.6±0.1 ms2 versus 3.9±1.3 ms2) than in wild-type mice. Baroreceptor-heart rate reflex sensitivity was significantly increased in AT2 receptor–deleted mice compared with wild-type mice (3.4±0.6 versus 2.1±0.5 ms/mm Hg). These differences remained after DOCA-salt and L-NAME treatments. We conclude that activation of the AT2 receptor impairs arterial baroreceptor reflex function, probably by a central action. These data support the existence of an inhibitory central effect of the AT2 receptor on baroreflex function.