Renal function and angiotensin AT1 receptor expression in young rats following intrauterine exposure to a maternal low-protein diet

Abstract

Recent studies have proposed a link between impaired nephrogenesis, decreased activity of the renin–angiotensin system and the onset of hypertension in rats exposed in the uterus to a maternal low-protein diet. However, there is no detailed information about renal function in this model; hence the aim of the present study was to assess renal function in young (4-week-old) rats exposed in the uterus to a maternal low-protein diet. Pregnant Wistar rats were fed isocalorific diets containing either 18% (normal protein; offspring denoted NP rats) or 9% (low protein; offspring denoted LP rats) (w/w) protein from conception until birth. At 4 weeks of age, male offspring were anaesthetized and prepared for the study of renal function, during which animals received saline alone, a bolus of enalapril (5 mg·kg-1) or a bolus of enalapril followed by an infusion of angiotensin II (30 ng·min-1·kg-1). Under control conditions, renal haemodynamic and tubular function did not differ. However, when challenged with angiotensin II, LP rats responded with a greater decrease in glomerular filtration rate than did NP rats [NP, 2.0±0.2 ml·min-1·g-1 kidney weight (n=9); LP, 1.0±0.2 ml·min-1·g-1 kidney weight (n=5); P<0.05]. Renal electrolyte excretion did not differ. LP rats had significantly fewer glomeruli than NP rats (P<0.01). Renal angiotensin II AT1 receptor expression was increased (P<0.01) by 24% in LP rats. It is concluded that blood pressure may be elevated in LP rats in order to maintain glomerular filtration rate against a background of fewer nephrons. Increased AT1 receptor expression, which may arise as a result of the direct effect of protein restriction or in response to the reported decrease in renal tissue angiotensin II concentration, could also contribute to the elevated blood pressure of this model.