Several studies in the Northeastern region of Brazil have demonstrated an association between hypertension in adult populations and prenatal and postnatal undernutrion. The central hypothesis we proposed was that hypertension could be favoured by programmed alterations in branches of the renal arachidonic pathway and consequently in counter-balancing the renin angiotensin system, especially during treatments with cyclooxygenase inhibitors. We assessed the influence of subchronic (21 days) and acute administration of nimesulide, a preferential cyclooxygenase-2 (COX-2) inhibitor, on mean blood pressure (MAP), renal blood flow (RBF), glomerular filtration rate (GFR) and urinary output (U v ) in adult rats that were prenatally undernourished. Undernutrition per se led to the onset of mild hypertension in adult offspring, whereas subchronic nimesulide treatment increased MAP in control and elicited further augmentation in undernourished animals. The drug (i) decreased RBF and GFR in controls by 50%, whereas no effect was detected in the undernourished group, and (ii) increased U v by 25% in controls, an effect that was potentiated by 200% in programmed animals. In contrast, acute nimesulide administration decreased U v , with the hypertensive effect of the drug being potentiated during dehydration. These findings demonstrate that prenatal nutritional programming differentially modulates adult renovascular responses to nimesulide in the cortex and medulla, which may exacerbate the deleterious effects of COX-2 inhibition in the kidney.Epidemiological studies indicate an association between undernutrition in early life and hypertension in adults in rural areas of Northeast Brazil [1]. Experimental undernutrition using a diet mimicking that widely used by human beings in these regions [2] leads to alterations in renal structure and function [3], including those related to angiotensin II-modulated renal fluid handling [4] that could be associated with the onset of hypertension in adulthood. Maternal dietary restriction using different protocols has demonstrated programming of renal lesions in cortex and medulla that could be involved in alterations of renovascular responses [5][6][7], although the role of the kidney in perinatal programming of long-term alterations of arterial blood pressure has had only minor attention until recently [8].Since the intrarenal renin ⁄ angiotensin II system might be modulated by arachidonic acid-derived vasoactive products reviewed in [9,10], we have postulated that programming of adult hypertension could also involve alterations in key steps of the renal arachidonic pathway, such as those mediated by cyclooxygenases. Consequently, the renovascular responses of adults become altered after undernourishment in early life. We also hypothesized that possible hidden alteration in the intrarenal arachidonic acid routes could be exacerbated during the treatment with cyclooxygenase inhibitors.The adult kidney is one of the few organs that constitutively produce cyclooxygenase-2 (COX-2), a...

Acetylsalicylic acid (ASA) during pregnancy reaches the fetus. It seems important to know possible repercussions of ASA on later renal function of the offspring, as well as repercussions of this drug on factors that may influence fetal development, such as maternal plasma volume and placental oxidative stress. It was evaluated whether ASA changes maternal plasma volume and/or placental oxidative stress, fetal weight and renal function of the offspring at adult life. ASA (100 mg/kg/day, p.o., dissolved in ETOH 10%) or ETOH 10% was administered to Wistar rat dams, from the day 7 to day 20 of pregnancy/parturition. Plasma volume and the placental oxidative stress were evaluated on day 20 of pregnancy, using, respectively, the Evans blue dye and the thiobarbituric acid reactive substances methods. Mean arterial pressure, renal blood flow (RBF) and glomerular filtration rate (GFR) were evaluated in the anesthetized offspring, at the age of 90 days, using a blood pressure transducer, a flow probe and inulin clearance respectively. Plasma volume was 76% (P < 0.05) higher in ASA compared with that in control dams, but placental oxidative stress was the same for both groups. Fetal body weight, the number of nephrons, GFR, RBF and renal vascular resistance were similar for the same gender among the offspring of the two groups. However, reduced hematocrit (9.8%, P < 0.05), increased renal plasma flow (27%, P < 0.05) and reduced filtration fraction (32%, P < 0.05) were seen in the female offspring. In conclusion, although ASA had increased maternal plasma volume, it did not change nephrogenesis nor GFR in the adult offspring. The changes in renal plasma flow and filtration fraction seen in the ASA female offspring might partially be due to the reduced hematocrit.