Intrauterine growth restriction (IUGR) may predispose offspring to an increased susceptibility of developing
cardiovascular disease (CVD) in adult life. The window of opportunity to treat later life CVD programmed in fetal life is critical. The aim of this study was to identify the effect of
resveratrol treatment of IUGR offspring at a time of known CV dysfunction. Sprague-Dawley male and female rat offspring who experienced normoxia (21% O2; control) or
hypoxia (11% O2; IUGR) in utero were fed a high-fat (HF) diet (3-21 weeks of age) or a HF diet (3-21 weeks of age) supplemented with
resveratrol from 13 to 21 weeks of age. At 21 weeks of age, echocardiographic data showed that male IUGR offspring had mild in vivo diastolic dysfunction, whereas female IUGR offspring had early signs of cardiac diastolic dysfunction that was not altered by
resveratrol treatment. Notably, male and female IUGR offspring demonstrated equal susceptibility to ex vivo cardiac dysfunction recovery after
ischemia/reperfusion (I/R) injury and this was improved by
resveratrol treatment, independent of sex.
Resveratrol increased cardiac phospho-
adenosine monophosphate kinase (p-AMPK) levels in only female IUGR offspring. IUGR or
resveratrol did not alter cardiac
superoxide levels. However, in male offspring, an overall effect of IUGR in reducing cardiac
catalase levels was observed that was not altered by
resveratrol. Interestingly, in only female IUGR offspring,
resveratrol significantly increased cardiac
superoxide dismutase (SOD) 2 levels. In conclusion,
resveratrol treatment of adult IUGR offspring, at the time of known CV dysfunction, improved cardiac function recovery in both sexes and the mechanisms involved were partially sex-specific.