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 3 – Effects of prenatal stress on monoamine oxidase A (MAO-A) mRNA at the apex and base of the left ventricle (LV) in the offspring. 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). 0.15 0.10 0.05 0.03 0.02 0.01 0.00 0.15 0.10 0.05 0.03 0.02 0.01 0.00 0.15 0.10 0.05 0.03 0.02 0.01 0.00 0.15 0.10 0.05 0.00 C C PS PS C PS C PS C PS Relative MAO A gene expression Relative MAO A gene expression Relative MAO A gene expression Relative MAO A gene expression Female offspring – LV apex Male offspring – LV apex Female offspring – LV base Male offspring – LV base A B C D apical and basal myocardium of left ventricle in female rat offspring from unstressed mothers. We also detected higher expression of ADRB1 compared to ADRB2 mRNA levels at the apical ventricular region in the control male offspring. Indeed, several human and other animal studies have demonstrated higher ADRB1 than ADRB2 density in left ventricle. 30-34 However, our results are not in accordance with the findings reported by Paur et al., 35 who used radioligand binding-displacement assays. They demonstrated increased ADRB2:ADRB1 ratio in the apical cardiomyocytes isolated from adult male Sprague Dawley rats. This discrepancy may be accounted for by different methods and model systems. Differently from in female offspring, ADRB1 and ADRB2 mRNA levels were similarly expressed in the left ventricular basal myocardium in male rat offspring. We did not detect ADRB3 mRNA in rat left ventricle. Our results suggest that there are sex- and region-specific gene expression representations of ADRB subpopulations within left ventricular rat myocardium. Additionally, data from our study indicate that prenatal stress may have affected ARB1 and ARB2 gene expression pattern at the apical region of the left ventricle in female offspring, but not in male offspring. Disturbed representation of cardiac adrenergic receptors subtypes has been described in cardiovascular pathologies. Heart failure is characterized by altered ADRB1:ADRB2 ratio, in part due to the decreased ADRB1 protein and mRNA within left ventricle. 11,36 The nonselective reduction of beta-adrenergic receptor subpopulations was also observed in the heart of both aged animals 37 and elderly patients. 31,34 Our results indicate that prenatal stress resulted in decreased apical ADRB1 mRNA expression suggesting that apical myocardial region of the female rat offspring might be sensitive to stress exposure during fetal life. Interestingly, higher sensitivity of the apical region within left ventricle to stress during adulthood has been described in Takotsubo (stress-induced) cardiomyopathy. 35,38 Moreover, this syndrome is predominantly diagnosed in women. 38 72