Role of Angiotensin II Type 1A Receptors in Cardiovascular Reactivity and Neuronal Activation After Aversive Stress in Mice

Abstract

We determined whether genetic deficiency of angiotensin II Type 1A (AT 1A ) receptors in mice results in altered neuronal responsiveness and reduced cardiovascular reactivity to stress. Telemetry devices were used to measure mean arterial pressure, heart rate, and activity. Before stress, lower resting mean arterial pressure was recorded in AT 1A −/− (85±2 mm Hg) than in AT 1A +/+ (112±2 mm Hg) mice; heart rate was not different between groups. Cage-switch stress for 90 minutes elevated blood pressure by +24±2 mm Hg in AT 1A +/+ and +17±2 mm Hg in AT 1A −/− mice ( P <0.01), and heart rate increased by +203±9 bpm in AT 1A +/+ and +121±9 bpm in AT 1A −/− mice ( P <0.001). Locomotor activation was less in AT 1A −/− (3.0±0.4 U) than in AT 1A +/+ animals (6.0±0.4 U), but differences in blood pressure and heart rate persisted during nonactive periods. In contrast to wild-type mice, spontaneous baroreflex sensitivity was not inhibited by stress in AT 1A −/− mice. After cage-switch stress, c-Fos immunoreactivity was less in the paraventricular ( P <0.001) and dorsomedial ( P =0.001) nuclei of the hypothalamus and rostral ventrolateral medulla ( P <0.001) in AT 1A −/− compared with AT 1A +/+ mice. Conversely, greater c-Fos immunoreactivity was observed in the medial nucleus of the amygdala, caudal ventrolateral medulla, and nucleus of the solitary tract ( P <0.001) of AT 1A −/− compared with AT 1A +/+ mice. Greater activation of the amygdala suggests that AT 1A receptors normally inhibit the degree of stress-induced anxiety, whereas the lesser activation of the hypothalamus and rostral ventrolateral medulla suggests that AT 1A receptors play a key role in autonomic cardiovascular reactions to acute aversive stress, as well as for stress-induced inhibition of the baroreflex.