Role of Angiotensin II in Cardiovascular Stress Responses in Rats Exposed to Glucocorticoids in Utero

Abstract

It is well known that even transient prenatal insults can impact cardiovascular function in adulthood. We have hypothesized that adult cardiovascular disease may have its origins in utero as a result of exposure to elevated levels of glucocorticoids. In support of this, we have shown that when pregnant rat dams are treated with the glucocorticoid, dexamethasone (DEX), for the last 4 days of gestation, female‐specific changes resulting in autonomic dysfunction and enhanced pressor and tachycardic responses to stress are detected in their adult offspring. Given the known role of angiotensin II in influencing the autonomic nervous system, the present study investigated the impact of angiotensin receptor antagonism on the cardiovascular stress responses in adult male and female rats that were exposed to DEX in utero. Pregnant dams were administered DEX (0.4 mg/kg per day, s.c.) or vehicle on gestation days 18–21. This resulted in a significant reduction in birthweight in DEX‐exposed males and females. At 2–3 months of age, arterial pressure was assessed via radiotelemetry. In order to assess whether prenatal DEX alters stress‐induced hypertensive and tachycardic responses, rats were placed in a restraint tube for 20 minutes, followed by a 2hr recovery period. Restraint‐stress testing was performed on diestrus in females. Restraint stress was then repeated following a 5‐day treatment with the angiotensin type 1 receptor antagonist, losartan (30 mg/kg per day, i.p). In female offspring, prenatal exposure to DEX resulted in enhanced elevations in systolic and diastolic pressure as well as heart rate in response to restraint stress relative to vehicle‐exposed rats. Treatment with losartan reduced the pressor and tachycardic responses to restraint, only in female rats that were prenatally exposed to DEX. In male rats, neither in utero exposure to DEX, nor losartan treatment altered the pressor or tachycardic response to stress in adult rats. These findings suggest that prenatal programming of cardiovascular disease due to exposure to glucocorticoids may be mediated in part due to long‐term changes in the renin angiotensin system, and this effect may be sex‐specific.Support or Funding InformationABRC ADHS14‐082990This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.