%0 Thesis %A Kenna, Kelly Rebecca %D 2017 %T Maternal ethanol consumption in late gestation : effects on vascular physiology in the offspring %U https://bridges.monash.edu/articles/thesis/Maternal_ethanol_consumption_in_late_gestation_effects_on_vascular_physiology_in_the_offspring/4774801 %R 10.4225/03/58d1d0fdbb73b %K Sheep %K Vascular physiology %K Small resistance arteries %K Fetus %K Physiology %K Fetal programming %K 2011 %K Vascular passive mechanical properties %K Restricted access and full embargo %K 1959.1/487800 %K Substance abuse %K Vascular development %K EtOH %K thesis(doctorate) %K Pregnancy %K ethesis-20110504-132812 %K Vascular function %K Postnatal %K Maternal alcohol %K monash:64586 %X Sixty percent of Australian women consume ethanol (EtOH) during pregnancy and/or lactation, with 10-15% drinking >2 standard drinks (e.g. >20g EtOH) in one sitting (Colvin et al., 2007). These statistics are concerning as maternal EtOH consumption is associated with detrimental effects in the offspring, the best known being cognitive dysfunction. The developing vascular system is vulnerable to developmental programming, but to date, the effects of fetal EtOH exposure on vascular physiology are largely unexplored. The aim of this study was to determine the effects of in utero EtOH exposure on regional vascular function in the offspring during fetal life and in the postnatal period. A model of maternal EtOH exposure in late gestation in pregnant sheep was used in which EtOH (0.75g/Kg; equivalent to 4-5 standard drinks) was infused into the maternal jugular vein over 1h daily from 95-133 days of gestation (term 147 days); this induced a peak plasma EtOH concentration of ~120mg/dL in the ewe and ~110mg/dL in the fetus, which declined to 0mg/dL over 8h. Saline infused sheep were used as controls. One cohort of pregnant ewes underwent recovery surgery to chronically implant fetuses with catheters and physiological probes at ~126 days of gestation for the measurement of a range of in vivo cardiovascular indices between 131 and 133 days of gestation. In this cohort, ewes and fetuses were killed at 134 days of gestation, 24hr after the final dose of EtOH. In a second cohort, fetuses were also exposed to EtOH from 95-133 days of gestation, and then ewes were allowed to give birth naturally at term. The lambs were raised with their mothers until necropsy at 9 weeks after birth. At 7 weeks after birth, these lambs underwent aseptic surgery for chronic implantation of catheters to assess in vivo vascular physiology at 8 weeks of age. At necropsy in both the fetal and postnatal groups, body and organ weights were measured and coronary, mesenteric, femoral, cerebral and renal resistance arteries collected for testing of vascular reactivity and passive mechanical properties using wire and pressure myographs, respectively. We observed that on days 131-133 of gestation (following ~37-39 days of EtOH exposure), there were transient decreases in maternal blood glucose concentration and pH and fetal oxygenation, and increased maternal and fetal blood lactate following each daily EtOH exposure. Fetal mean arterial pressure, heart rate and birth weight were not affected, although fetal heart weights were greater than control fetuses. These findings indicate that repeated EtOH exposure alters the physiology of both the mother and fetus without inducing fetal growth restriction, nor affecting fetal mean arterial pressure or heart rate. In the postnatal group, birth weight at term was unaffected by EtOH exposure and postnatal growth was also unaffected for up to 9 weeks of postnatal life. Mean arterial pressure and heart rate were unaffected by prenatal EtOH exposure in the postnatal lamb group, although the aortic/femoral pulse wave velocity was decreased in the EtOH treatment group, indicating a decrease in arterial wall stiffness. Our findings demonstrate that this model of fetal EtOH exposure induces changes in fetal and postnatal physiology. In the EtOH exposed fetuses and postnatal lambs, we observed region-dependent differences in vascular function across a range of small arteries from the coronary, mesenteric, femoral, cerebral and renal beds. In fetuses, EtOH exposure led to endothelial vasodilator dysfunction in coronary vessels, but increased vasodilation in mesenteric and renal vessels. Responsiveness to vasoconstrictors was increased in coronary blood vessels and decreased in renal and cerebral blood vessels. In postnatal femoral and renal arteries from lambs exposed to EtOH before birth, endothelium-dependent relaxation was decreased and the ability of the smooth muscle to relax when challenged with exogenous nitric oxide was also decreased. Fetal EtOH exposure had region-specific effects on vascular function in fetuses and postnatal lambs following withdrawal of EtOH. Overall, the changes observed in postnatal endothelial and smooth muscle function are likely to increase the risk of vascular dysfunction in later life. Fetal EtOH exposure caused a global increase in arterial wall stiffness in coronary, mesenteric, femoral, cerebral and renal arteries in the late gestation fetus. In addition, we observed increases in collagen Iα1 mRNA expression in mesenteric, renal and cerebral vessels and tropoelastin mRNA expression in cerebral arteries compared with controls. In postnatal lambs exposed to EtOH before birth, arterial wall stiffness remained greater in mesenteric, renal and cerebral vessels, but was decreased in coronary and femoral arteries compared with controls. Prenatal EtOH exposure had long term effects on passive mechanical properties which could predispose individuals to hypertension and other cardiovascular diseases in later life. We conclude that daily EtOH exposure during late gestation causes transient changes in fetal and maternal physiology. Fetal EtOH exposure induces major region-dependent effects on vascular function and wall properties mechanics before and after birth. Collectively, prenatal EtOH exposure changes the functional and passive mechanical wall properties of small arteries in a manner that could predispose individuals to cardiovascular disease in adulthood. These changes occurred with levels of EtOH exposure that did not indicate physical deformity, which is associated with excessive exposure. This study provides experimental evidence to support the importance of women avoiding modest alcohol consumption during pregnancy, due to the potential detrimental impact of EtOH on the developing vascular system. %I Monash University