on November 2, 2009
Published online before print November 2, 2009, doi: 10.1161/HYPERTENSIONAHA.109.139741
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Submitted on July 23, 2009
From the Baker IDI Heart and Diabetes Institute (P.J.D., G.A.H.), Melbourne, Victoria, Australia; Departments of Physiology (D.C.) and Pharmacology (C.A.C., D.N.M.), University of Melbourne, Victoria, Australia; Centre for Biomedical Sciences (T.W.), Hull York Medical School, University of Hull, Hull, United Kingdom; Excellence Cluster Cardio-Pulmonary System (T.W.), Justus-Liebig-Universität Giessen, Giessen, Germany. * To whom correspondence should be addressed. E-mail: geoff.head{at}bakeridi.edu.au.
Abstract—We determined whether genetic deficiency of angiotensin II Type 1A (AT1A) 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 AT1A-/- (85±2 mm Hg) than in AT1A+/+ (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 AT1A+/+ and +17±2 mm Hg in AT1A-/- mice (P<0.01), and heart rate increased by +203±9 bpm in AT1A+/+ and +121±9 bpm in AT1A-/- mice (P<0.001). Locomotor activation was less in AT1A-/- (3.0±0.4 U) than in AT1A+/+ 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 AT1A-/- 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 AT1A-/- compared with AT1A+/+ 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 AT1A-/- compared with AT1A+/+ mice. Greater activation of the amygdala suggests that AT1A receptors normally inhibit the degree of stress-induced anxiety, whereas the lesser activation of the hypothalamus and rostral ventrolateral medulla suggests that AT1A receptors play a key role in autonomic cardiovascular reactions to acute aversive stress, as well as for stress-induced inhibition of the baroreflex.
Revised on August 9, 2009
Role of Angiotensin II Type 1A Receptors in Cardiovascular Reactivity and Neuronal Activation After Aversive Stress in Mice
Pamela J. Davern;
Key words: receptors • angiotensin II • stress • blood pressure • heart rate • immunohistochemistry • mice