Previous studies have shown that feeding a low protein diet to rats during pregnancy induces a significant increase in mean arterial pressure (MAP) of the offspring (Langley-Evans et al. 1994). The role of the kidney and the renin-angiotensin system have not yet been fully described in this model of hypertension. Accordingly, we have measured the renal response to angiotensin II (Ang II) of pups exposed to either a 9 % or 18 % protein diet in utero.

In utero protein restriction was induced by feeding female Wistar rats a diet containing 9 % protein, compared with an isocalorific 18 % protein diet for control animals, from the day of conception until birth (Langley-Evans et al. 1994). Immediately after birth, dams and pups were fed with a standard maintenance diet. At 4 weeks of age, pups were prepared for standard clearance measurements under Intraval anaesthesia (thiopentone sodium, 110 mg kg^-1; I.P.). During a 2 h equilibration period rats received a continuous intravenous infusion of 0.9 % saline, containing [³H] inulin (0.3 µCi h^-1), PAH (3 mg h^-1) and 4.6 % bovine serum albumin, at a rate of 50 µl min^-1 (100 g body weight)^-1. Rats then either received saline and clearance markers only, or a bolus dose of angiotensin converting enzyme inhibitor enalapril (enalapril maleate, 5 mg kg^-1; I.V.) 30 min prior to clearance measurements or a bolus dose of enalapril followed by Ang II (1800 ng kg^-1 h^-1) for a further hour, after which they were humanely killed.

MAP of 9 % protein rats was significantly higher than that of control 18 % protein rats (18 %, n = 12, 76 ± 3 mmHg vs. 9 %, n = 12, 102 ± 4 mmHg, P < 0.001). MAP did not alter after enalapril administration nor during the infusion of Ang II. Under control conditions renal function was similar in both groups of rats. Urine output and renal blood flow were not influenced by the administration of enalapril nor the infusion of Ang II. However, Ang II induced a significant (P < 0.05) reduction in glomerular filtration rate in 9 % protein compared with 18 % protein pups.

These data suggest that renal sensitivity to Ang II may be enhanced in rats exposed to low protein in utero, which may contribute to the elevated blood pressure observed in these rats as early as 4 weeks of age.

Langley-Evans, S.C., Philips, G.J. & Jackson, A.A. (1994). Clin. Nutr. 13, 319-324.