TY - JOUR
T1 - Impact of Angiotensin II Receptor Antagonism on the Sex-Selective Dysregulation of Cardiovascular Function Induced by in Utero Dexamethasone Exposure
AU - Madhavpeddi, L.
AU - Hammond, B.
AU - Carbone, D. L.
AU - Kang, P.
AU - Handa, R. J.
AU - Hale, Taben M.
N1 - Publisher Copyright:
© 2022 American Physiological Society. All rights reserved.
PY - 2022/7
Y1 - 2022/7
N2 - In utero exposure to glucocorticoids in late gestation programs changes in cardiovascular function. The objective of this study was to determine the degree to which angiotensin II mediates sex-biased changes in autonomic function as well as basal and stress-responsive cardiovascular function following in utero glucocorticoid exposure. Pregnant rats were administered the synthetic glucocorticoid dexamethasone (DEX 0.4mg/kg per day, s.c.) or vehicle on gestation days 18-21. Mean arterial pressure, heart rate, and heart rate variability (HRV) were measured via radiotelemetry in freely moving, conscious adult rats. To evaluate the impact of stress, rats were placed in a restraint tube for 20 minutes. In a separate cohort of rats, restraint stress was performed before and after chronic treatment with the angiotensin type 1 receptor antagonist, losartan (30mg/kg per day, i.p). Frequency domain analysis of HRV was evaluated, and data integrated into low frequency (LF: 0.20-0.75Hz) and high frequency (HF: 0.75-2.00Hz) bands. Prenatal DEX resulted in an exaggerated pressor and heart rate response to restraint in female offspring that was attenuated by prior losartan treatment. HF power was higher in vehicle-exposed female rats, compared to DEX females. Following losartan, HF power was equivalent between female vehicle and DEX-exposed rats. In utero exposure to DEX produced female-biased alterations in stress-responsive cardiovascular function which may be indicative of a reduction in parasympathetic activity. Moreover, these findings suggest this autonomic dysregulation may be mediated in part by long-term changes in renin-angiotensin signaling.
AB - In utero exposure to glucocorticoids in late gestation programs changes in cardiovascular function. The objective of this study was to determine the degree to which angiotensin II mediates sex-biased changes in autonomic function as well as basal and stress-responsive cardiovascular function following in utero glucocorticoid exposure. Pregnant rats were administered the synthetic glucocorticoid dexamethasone (DEX 0.4mg/kg per day, s.c.) or vehicle on gestation days 18-21. Mean arterial pressure, heart rate, and heart rate variability (HRV) were measured via radiotelemetry in freely moving, conscious adult rats. To evaluate the impact of stress, rats were placed in a restraint tube for 20 minutes. In a separate cohort of rats, restraint stress was performed before and after chronic treatment with the angiotensin type 1 receptor antagonist, losartan (30mg/kg per day, i.p). Frequency domain analysis of HRV was evaluated, and data integrated into low frequency (LF: 0.20-0.75Hz) and high frequency (HF: 0.75-2.00Hz) bands. Prenatal DEX resulted in an exaggerated pressor and heart rate response to restraint in female offspring that was attenuated by prior losartan treatment. HF power was higher in vehicle-exposed female rats, compared to DEX females. Following losartan, HF power was equivalent between female vehicle and DEX-exposed rats. In utero exposure to DEX produced female-biased alterations in stress-responsive cardiovascular function which may be indicative of a reduction in parasympathetic activity. Moreover, these findings suggest this autonomic dysregulation may be mediated in part by long-term changes in renin-angiotensin signaling.
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U2 - 10.1152/AJPHEART.00587.2021
DO - 10.1152/AJPHEART.00587.2021
M3 - Article
C2 - 35179975
AN - SCOPUS:85127729198
SN - 0363-6135
VL - 322
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 4
ER -