ABC | Volume 112, Nº1, January 2019

Original Article Jevjdovic et al Prenatal stress affects rat heart ADRB1 Arq Bras Cardiol. 2019; 112(1):67-75 Figure 2 – Effects of prenatal stress on expression of beta 1 (ADRB1) and beta 2 (ADRB2) adrenergic receptors mRNA at the apex and base of the left ventricle in the offspring (LV). Results are presented for female (A and C) and male (B and D) offspring from unstressed (control-C) and stressed mothers (prenatal stress-PS). Data are expressed as median with interquartile range (number of animals per group, n = 5-8 per group). *p < 0.05; **p < 0.01, Mann-Whitney U-test 0.04 0.03 0.02 0.01 0.00 Relative gene expression 0.04 0.03 0.02 0.01 0.00 Relative gene expression 0.04 0.03 0.02 0.01 0.00 Relative gene expression 0.04 0.03 0.02 0.01 0.00 Relative gene expression ADRB1 ADRB2 ADRB1 ADRB2 ADRB1 ADRB2 ADRB1 ADRB2 Female offspring – LV apex Male offspring – LV apex Female offspring – LV base Male offspring – LV base A B C D C PS ** ** ** ** * Discussion Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. 23 It has been shown that various disturbances of fetal development may contribute to development of cardiovascular disorders in adulthood. Offspring from stressed mothers or mothers undergoing glucocorticoid therapy during pregnancy display various neuroendocrine and behavioral alterations during adulthood. 24-26 This study examined expression of ADRB subtypes and MAO-A in different regions of the left ventricle in the offspring of both sexes prenatally exposed to maternal stress. We applied stress protocol to pregnant rat females that could potentially mimic everyday life stress that pregnant females are exposed to. Our stress protocol involved chronic exposure to various mild stressors which prevents habituation, which can be observed after repeated exposure to the same stressor. 27 Plasma ACTH level was increased in stressed mothers compared to pregnant unstressed rats, which indicated that HPA axis activity of pregnant females was increased by the CUMS protocol, which is consistent with previous studies. 28,29 We did not observe any significant difference in metabolic parameters such as maternal weight gain during pregnancy, water and food consumption, or blood glucose level between stressed and unstressed mothers. Nor did maternal stress during the last week of pregnancy affect litter size or birth weight. Taken together, these results imply that our model of CUMS was potent enough to induce a stress response in pregnant rats but did not affect offspring weight, which is known to be one of the risk factors for development of adult cardiovascular disorders. 2 To the best of our knowledge, this is the first study to report relative gene expression levels of beta-adrenergic receptor subtypes in two different regions within rat left ventricle. Our results show that ADRB1 is the predominantly expressed subtype of the cardiac ADRB population at 71