Heart rate variability and baroreflex function in AT2 receptor-disrupted mice

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 (AT(2)) receptor-deleted (AT(2) -/-) and wild-type (AT(2) +/+) mice with either deoxycorticosterone acetate (DOCA)-salt hypertension or Nomega-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 AT(2) 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 AT(2) receptor-deleted mice with L-NAME to 114 +/- 1 rum Hg (day) and 121 +/- 1 mmHg (night), compared with 105 +/- 2 mmHg (day) and 111 +/- 2 mmHg (night), respectively. DOCA-salt also increased day and night blood pressures in AT(2) 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 AT(2) receptor-deleted mice and AT(2) receptor-deleted mice at baseline. Systolic blood pressure variability in the low frequency band was lower in AT(2) receptor-deleted mice (0.6 +/- 0.1 ms(2) versus 3.9 +/- 1.3 ms(2)) than in wild-type mice. Baroreceptor-heart rate reflex sensitivity was significantly increased in AT(2) 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 AT(2) receptor impairs arterial baroreceptor reflex function, probably by a central action. These data support the existence of an inhibitory central effect of the AT(2) receptor on baroreflex function.