Prenatal undernutrition changes renovascular responses of nimesulide in rat kidneys

Several studies in the Northeastern region of Brazil have demonstrated an association between hypertension in adult populations and prenatal and postnatal undernutrition. 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.