Abstract
Our previous studies have demonstrated the programmed impairment of sodium excretion in lean antenatal betamethasone exposed sheep whereby the males exhibited blunted excretion of a sodium load when compared to control males or control or antenatal betamethasone exposed females. Obesity has been recognized as a risk factor for developing early stage kidney failure in individuals exposed to unfavorable intrauterine conditions by virtue of fetal programming. We hypothesize that obesity (second hit) can accentuate the impairment of sodium excretion in antenatal betamethasone exposed offspring in a sex specific manner. Pregnant ewes received either betamethasone or vehicle at 80-81 days gestation. The male (n=6 per group) or female (n=5 per group) offspring were overfed to become obese (40% weight gain over a course of 3 months) at age of 1.5 years. Acute sodium load (sodium chloride: 0.13g/kg) was administrated intravenously. Sodium excretion (excreted sodium load), blood pressure (BP), renal plasma flow (RPF), and glomerular filtration rate (GFR) were measured. Data for sodium excretion are expressed as percentage of excreted sodium load. ANOVA and Student’s t test were used for data analysis. The excreted sodium load was lower in obese male antenatal betamethasone exposed offspring (OMB) than in obese male vehicle exposed offspring (OMV) (13.5±3.1% vs. 33.2±9.9% p=0.04). However, the excreted sodium load was not significantly different between obese female antenatal betamethasone exposed offspring (OFB) and obese female vehicle exposed offspring (OFV) (60.4±6.2% vs. 72.0±8.2%, p=0.31). Compared male offspring with female offspring, the excreted sodium load was lower in male offspring (33.2±9.9% vs. 72.0±8.2%, p=0.001, OMV vs. OFV; 13.5±3.2% vs. 60.4±6.2%, p<0.0001, OMB vs. OFB). During the experiments BP, RPF and GFR did not change significantly. . These data suggest that obesity, acting as a second hit, accentuates impairment of sodium excretion in antenatal betamethasone exposed male but not female offspring. Thus the sex specific effect of antenatal betamethasone on sodium excretion persists in in animals experiencing a secondary insult of obesity in adulthood.
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