Pharmacologic and Endotoxic Reprogramming of Renal Vasodilatory, Inflammatory, and Apoptotic Blemishes in Weaning Preeclamptic Dams

Abstract ID 87658 Poster Board 471 Preeclampsia (PE) and peripartum sepsis are two considerable complications of pregnancy and often associated with disturbed renal function. Here we investigated whether hemodynamic and renal vasodilatory aberrations induced by PE in rats could be modulated by endotoxic or pharmacotherapeutic challenges. The preeclamptic rises in systolic blood pressure and urine protein induced by gestational administration of the nitric oxide synthase inhibitor L-NAME (50 mg/kg/day for 7 days) were significantly attenuated after simultaneous treatment with losartan or pioglitazone. These drugs further improved the impaired dose-dependent vasodilatory responses evoked by adenosinergic (N-ethylcarboxamidoadenosine, 1.6–100 nmol) or cholinergic (acetylcholine, 0.01-7.29 nmol) receptor activation in isolated perfused kidneys of weaning PE dams. Likewise, the exposure of weaning PE dams to a single 4-hr dosing of the endotoxic challenge (lipopolysaccharides, LPS, 5 mg/kg) enhanced renal vasodilation and accentuated the upregulated vasodilatory response set off by gestational losartan or pioglitazone. Molecularly, the privileged action of pharmacologic or endotoxic intervention against the adverse renal response to PE was coupled with dampened tubular and glomerular expressions of inflammatory (toll-like receptor 4) and apoptotic signals (caspase-3). Together, our data unveil favorable and possibly intensified conditioning effect for endotoxemia when combined with losartan or pioglitazone against renovascular dysfunction and inflammation induced by PE.