Perinatal growth restriction decreases diuretic action of furosemide in adult rats
- Publication date
- Publisher
- 'Elsevier BV'
Abstract
Perinatal growth restriction programs higher risk for chronic disease during adulthood
via morphological and physiological changes in organ systems. Perinatal growth
restriction is highly correlated with a decreased nephron number, altered renal function
and subsequent hypertension. We hypothesize that such renal maladaptations result in
altered pharmacologic patterns for life. Maternal protein restriction during gestation and
lactation was used to induce perinatal growth restriction in the current study. The
diuretic response of furosemide (2mg/kg single i.p dose) in perinatally growth restricted
rats during adulthood was investigated. Diuresis, natriuresis and renal excretion of
furosemide were significantly reduced relative to controls, indicative of decreased
efficacy. While a modest 12% decrease in diuresis was observed in males, females
experienced 26% reduction. It is important to note that the baseline urine output and
natriuresis was similar between treatment groups. The in vitro renal and hepatic
metabolism of furosemide, the in vivo urinary excretion of the metabolite, and the
expression of renal drug transporters was unaltered. Creatinine clearance was
significantly reduced by 15% and 19% in perinatally growth restricted male and female
rats, respectively. Further evidence of renal insufficiency was suggested by decreased
uric acid clearance. Renal protein expression of sodium-potassium-chloride
cotransporter, a pharmacodynamic target, was unaltered. In summary, perinatal growth
restriction could permanently imprint pharmacokinetic processes affecting drug
response.Keywords: perinatal growth restriction, furosemide, pharmacokinetics, fetal programming, renal insufficiency, in utero growth restrictio