Maternal renal dysfunction in sheep is associated with salt insensitivity in female offspring

Abstract

To examine the programming effects of maternal renal dysfunction (created by subtotal nephrectomy in ewes prior to mating; STNx), renal and cardiovascular function were studied in 6-month-old male and female offspring of STNx and control pregnancies. After studies were conducted on a low salt diet (LSD) some female offspring underwent salt loading (0.17 M NaCl in the drinking water for 5-7 days; HSD). On LSD both male and female offspring of STNx had similar mean arterial pressures (MAP), heart rates, cardiac outputs and renal function to those measured in offspring of control ewes. In female STNx offspring on a HSD, plasma sodium levels increased and haematocrits fell, indicating volume expansion (P < 0.05). Plasma renin levels were not suppressed despite the increases in plasma sodium concentrations, but aldosterone levels were reduced. In control animals plasma renin levels fell (P < 0.05) but there was no change in plasma aldosterone concentrations. There was a positive relationship between GFR and MAP which was present only in female STNx offspring. In conclusion, in STNx offspring there was an impaired ability to regulate glomerular filtration independent of arterial pressure, renin release was insensitive to a high salt intake and control of aldosterone secretion was abnormal. This study provides evidence of abnormal programming of the renin-angiotensin system and glomerular function in offspring of pregnancies in which there is impaired maternal renal function.

Figure 1

Haematocrit in 6-month-old female offspring of control (filled) or subtotally nephrectomised ewes (STNx, hatched) studied under conditions of low (LSD) and high salt (HSD) diets #Difference between groups on LSD, P < 0.05; *different from LSD, P < 0.05; ‡interaction between mother (control or STNx) and salt intake, P < 0.05. Values are means ±s.e.m.

Figure 2

Plasma sodium levels (A) and plasma potassium levels (B) in 6-month-old female offspring of control (filled, n= 5) or subtotally nephrectomised ewes (STNx, hatched, n= 6) studied under conditions of low (LSD) and high salt (HSD) diets *Different from LSD, P < 0.05. Values are means ±s.e.m. Control, n= 5; STNx, n= 6.

Figure 3

Plasma renin levels (A) and plasma aldosterone levels (B) in 6-month-old female offspring of control (filled, n= 5) or subtotally nephrectomised ewes (STNx, hatched, n= 6) studied under conditions of low (LSD) and high salt (HSD) diets *Different from LSD, P < 0.05. Values are means ±s.e.m. Control, n= 5; STNx, n= 6.

Figure 4

The relationship between glomerular filtration rate (GFR) (A), effective renal plasma flow (B) and the excretion of sodium (E_Na) and mean arterial pressure (MAP) (C) in 6-month-old female offspring born to either control (○) or STNx ewes (▴) on both a low and high salt diet *Difference between control and STNx, P < 0.05. A and B, control n= 20 data points and STNx n= 24 data points (2 points per animal per diet). C, control n= 40 data points and STNx n= 48 data points (4 points per animal per diet).