"Imprinting" Mechanism Underlying Impact Of Maternal Dehydration During Mid-term Gestation On Body Fluid And Cardiovascular Homeostasis In Adult Offspring

Partâ… Influence of body fluid homeostasis in adult offspring induced by maternal dehydration in mid-term gestation[Objectives]To investigate the impact on body homeostasis in adult offspring induced by maternal dehydration during mid-term gestation[Methods]Blood electrolytes and plasma osmolarity were determined using a Nova analyzer and an advanced digmatic osmometer,respectively,in adult offspring.Water intake and sodium appetite of adult offspring were detected after 48h water deprivation or intracerebroventricular injection of Angâ…¡.The alteration of blood pressure,in adult offspring,was observed after 48h water deprivation with the method of femoral artery cannulation.With the application of histological immunochemical staining,expression and distribution of AT1 and AT2 receptors in the kidney were assessed;and the c-Fos positive nuclei,induced by 48h water deprivation,in several concerned brain region were counted, in the adult offspring.The mRNAs of AT1 a,AT1 b and AT2 receptors in the kidney of adult offspring were semi-quantified using real-time RT-PCR.[Results]In basal condition,blood Na⁺ concentration and plasma osmolarity in WD adult offspring(whose mother was suffered 72h water deprivation in mid-term gestation) were significantly elevated compared with those in control(whose mother was not be stimulated in gestation period).After 48 water deprivation,the WD adult offspring drank less water but more saline(1.8%NaCl) than that of control;c-Fos positive nuclei in several concemed brain regions were significantly increased in WD adult offspring compared to those in control.MAP(mean arterial blood pressure) in WD adult offspring was not changed after 48h water deprivation;however,MAP was significantly elevated in control. The expression of AT1 and AT2 receptors and mRNAs of AT1a,AT1b,and AT2 in the kidney of WD adult offspring were significantly increased compared with those in control. There appeared somewhat pathological changes in the kidney of WD adult offspring.[Conclusions]The "imprinting" effects were emerged resulted from the stimulus of maternal water deprivation in the mid-term gestational period.Partâ…¡Impact of cardiovascular regulation in adult offspring induced by maternal dehydration in mid-term gestation[Objectives]To explore the influence of cardiovascular system in adult offspring resulted from maternal water deprivation in mid-term gestation[Methods]MAP responses induced by intravenous injection of Angâ…¡,Losartan, PD123319,and intracerebroventricular administration of Angâ…¡,were assessed in adult offspring using femoral artery/vein cannulation.In thoracic aorta of adult offspring, dose-response effects triggered by Angâ…¡and PE were determined;influences of PE- and Angâ…¡-induced contraction affected by L-NAME was assessed;meanwhile,alteration of Angâ…¡-induced contraction was also observed under the application of Losartan or PD123319.In mesenteric arteriole of adult offspring,besides the experiments parallel with those in the aortic vessel ring,the dose-response effects triggered by Angâ…¡and PE influenced by CTX were also determined.In mesenteric arteriole of adult offspring,the responses of free intracellular Ca²⁺ concentration([Ca²⁺]_i) triggered by PE and Angâ…¡were tested using IonOptix Ca²⁺ imaging system.Expression and distribution of AT1 and AT2 receptors in thoracic aorta and heart,and mRNA ofATla,AT1b and AT2 receptors in heart of adult offspring were observed with the method of histological immunochemical staining and real-time RT-PCR,respectively.[Results]MAP response to peripheral Angâ…¡in WD adult offspring was stronger than that in control;in addition,the duration of pressor effect in WD adult offspring induced by central Angâ…¡was significantly elongated compared with that in control.In WD offspring, MAP responses to intravenous injection of Losartan and PD123319 were little changed; however,in control offspring,Losartan-triggered MAP decline and PD123319-induced MAP elevation were both existed.In both thoracic aorta and mesenteric arteriole of WD adult offspring,PE- and Angâ…¡-induced contraction responses were all changed compared to those of control.Furthermore,NO- and BK channel-mediated dilation effects induced by PE and Angâ…¡were also changed in WD adult offspring compared to those in control.In mesenteric arteriole of WD adult offspring,PE- and AnglI-induced responses of[Ca²⁺]_i elevation were significantly enhanced compared with that of control.The expression of AT1 and AT2 receptors in either thoracic aorta or heart,and mRNAs ofAT1a,AT1b,and AT2 in the heart of WD adult offspring,were significantly increased compared with those in control.Somewhat pathological changes were also observed in both thoracic aorta and heart of WD adult offspring.[Conclusions]"Imprinting" effects,underlying both functional and structural changes involving regulation of cardiovascular system,were induced by the prenatal insults of maternal water deprivation in mid-term gestational period.As a result,the risk concerning several cardiovascular diseases(e.g.hypertension) in WD adult offspring could be increased.