P10.06 ABNORMAL VASCULAR PROGRAMMING OF ACID ARACHIDONIC METABOLISM COULD EXPLAIN HYPERTENSION IN RATS EXPOSED IN UTERO TO MATERNAL DIABETES

Epidemiologic studies have clearly demonstrated that cardiovascular risk is not only determined by conventional risk factors of importance in adult life, but also by early life events resulting of re-settings of key physiological functions. In our model of rats exposed in utero to maternal diabetes, we previously identified a specific gene expression profile of the thoracic aorta at a pre-hypertensive stage (3 months) in favour of vasoconstriction, which could explain the development of hypertension in the adult offsprings. We found an increase of CYP4f2 (however we failed to confirm its up-regulation at the protein level), and a decrease by 50 percent of the prostacyclin (IP) receptor at messenger and protein levels in aorta of rats exposed to maternal diabetes (DMO) compared to rats from control mothers (CMO). We demonstrated the functional implication of this down-expression of the IP receptor in a pharmacological study using a prostacyclin analogue: Iloprost (iv, 4 ng/kg/ml). Indeed, we showed that, even before the onset of hypertension, SBP reduction in response to Iloprost was attenuated in DMO rats (−10.7% vs −21.3% in CMO, p