Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats

Abstract

ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7-22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60 -68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 with plasma samples taken before and at three 40-min intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were ϳ20% greater in PEexposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PEexposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus. fetal alcohol syndrome; vasopressin; plasma osmolality; thirst; vasopressin messenger ribonucleic acid; neurohypophysis CHRONIC CONSUMPTION of alcohol has been shown to significantly reduce the number of AVP-producing neurons in the rat supraoptic nucleus (19). More recently, chronic alcoholism in humans has also been shown to reduce AVP-producing neurons in a dose-related and time-dependent manner (13). Furthermore, AVP synthesis is reduced, as evidenced by reduced AVP mRNA in the hypothalamus of rats chronically administered alcohol, and there is a reduced AVP mRNA response to an osmotic stimulus in similarly treated rats (28). Correspondingly, chronic exposure to alcohol in humans has been reported to reduce plasma levels of AVP (7, 14) and cerebrospinal fluid levels of AVP (23). Thus the AVP system would appear to be impaired by chronic alcohol exposure in adult rats and humans.Previous work has also demonstrated that brain weight is reduced in adult rats that were prenatally exposed to ethanol during the second half of pregnancy (29), and other studies have demonstrated a dose dependence of alcohol-induced brain damage and that some brain structures are more sensitive to the damage than others (21). More specifically, Rojas-Castaneda et al. (26) have reported evidence of morphological changes in the AVP-producing cells of the suprachiasmatic nucleus of 15-dayold rats that were prenatally exposed to ethanol. However, the number of AVP-producing cells was not observed to be significantly reduced in similar studies by the same group (27).Last, there is evidence that AVP systems are nearly fully developed during gestation. AVP has bee...

Pituitary lacks sexual dimorphism and displays reduced signal intensity on T1-weighted MRI in adolescents with histories of heavy prenatal alcohol exposure

“…Both the brain and systemic responses appear to be impacted by prenatal alcohol exposure to alter these homeostatic responses (Godino et al, 2015). Importantly, pituitary vasopressin content was reduced in rats with prenatal alcohol exposure (Knee et al, 2004; Bird et al, 2006), which is consistent with our observations of reduced signal intensity in the pituitary. Vasopressin is involved in hormone secretion from the anterior pituitary, water reabsorption in the kidneys, and cardiovascular homeostasis (Koshimizu et al, 2012).…”

“…Animal studies indicate that prenatal alcohol exposure produce changes in vasopressin release and fluid homeostasis (Dow-Edwards et al, 1989). Prenatal alcohol exposed rats show increased water consumption and urinary output along with changes to osmotic- or hemorrhage- stimulated vasopressin release (McGivern et al, 1998; Knee et al, 2004; Bird et al, 2006). Both the brain and systemic responses appear to be impacted by prenatal alcohol exposure to alter these homeostatic responses (Godino et al, 2015).…”

Prenatal Exposure to Alcohol Reduces Nephron Number and Raises Blood Pressure in Progeny

“…Similar models of maternal ethanol exposurefindthatmaximalBACrangesfrom0.13to0.2g/dlwhenalcohol is presented to animals in their drinking water or administered by gavage. 21,22 The timing of ethanol exposure in this study relates to the earliest stages of kidney development, when the ureteric bud has just started to invade the metanephric mesenchyme. This corresponds to Figure 3.…”

Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension inBr/+ adult mice

“…Mean arterial pressure (MAP) measurement, heart rate (HR) recording, and blood sampling were performed on conscious animals after carotid artery catheter implantation, based on the procedure we previously described for rats (15,53). Briefly, mice were anesthetized with isoflurane (1-3% in oxygen) administered via a gas mask Plexiglas tube modified for mice.…”