Role of angiotensin II Type 1A receptors in cardiovascular reactivity and neuronal activation after aversive stress in mice.
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.
Davern
Pamela J
PJ
Baker IDI Heart and Diabetes Institute, Commercial Rd, Prahran, PO Box 6492, St. Kilda Road Central, Melbourne, Victoria 8008, Australia.
Chen
Daian
D
Head
Geoffrey A
GA
Chavez
Carolina A
CA
Walther
Thomas
T
Mayorov
Dmitry N
DN
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D001808:Blood Vessels / Q000294:innervation / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D013610:Tachycardia / Q000378:metabolism / Q000503:physiopathology; D013686:Telemetry
D016760:Proto-Oncogene Proteins c-fos; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II