Conclusion
Preeclamptic fetal programming of endotoxic hemodynamic and renal manifestations in adult offspring depends on animal sex and specific biological activity and are reprogrammed by antenatal pioglitazone/losartan therapy.
Methods
PE was induced by oral administration of L-NAME (50 mg/kg/day) for the last 7 days of pregnancy. Adult offspring was treated with lipopolysaccharides (LPS, 5 mg/kg) followed 4-h later by hemodynamic and renovascular studies.
Results
Tail-cuff measurements showed that LPS decreased systolic blood pressure (SBP) in male, but not female, offspring of PE dams. Moreover, PE or LPS reduced vasodilations elicited by acetylcholine (ACh, 0.01-7.29 nmol) or N-ethylcarboxamidoadenosine (NECA, 1.6-100 nmol) in perfused kidneys of male rats only. The latter effects disappeared in LPS/PE preparations, suggesting a postconditioning action for LPS against renal manifestation of PE. Likewise, elevations caused by LPS in serum creatinine and inflammatory cytokines (TNFα and IL-1β) as well as in renal protein expression of monocyte chemoattractant protein-1 (MCP-1) and AT1 receptors were attenuated by the dual PE/LPS challenge. Gestational pioglitazone or losartan reversed the attenuated ACh/NECA vasodilations in male rats but failed to modify LPS hypotension or inflammation. The combined gestational pioglitazone/losartan therapy improved ACh/NECA vasodilations and eliminated the rises in serum IL-1β and renal MCP-1 and AT1 receptor expressions.