Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy

Abstract

Evidence from human and animal studies suggests that maternal nutrition can induce developmental programming of adult hypertension in offspring. We have previously described a model of maternal dietary imbalance in Sprague-Dawley rats whereby administration of a maternal diet rich in animal lard programmes the development of increased blood pressure, insulin resistance, dyslipidaemia, obesity and mesenteric artery endothelial dysfunction in adult offspring. To further characterize the mechanism of hypertension in this model we have examined vascular and renal structure in adult offspring of Sprague-Dawley rats fed a control diet (OC) or lard-rich diet (OHF) during pregnancy and suckling followed by a control diet post-weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na+,K+-ATPase activity. Plasma aldosterone concentration was also measured. Stereological examination of the aorta in OHF demonstrated reduced endothelial cell volume and smooth muscle cell number compared with OC. Adult OHF animals showed increased aortic stiffness and reduced endothelium-dependent relaxation. Renal stereology showed no differences in kidney weight, glomerular number or volume in OHF compared with OC, but renin and Na+,K+-ATPase activity were significantly reduced in OHF compared with controls. Programmed alterations to aortic structure and function are consistent with previous observations that exposure to maternal high fat diets produces systemic vascular changes in the offspring. Despite normal renal stereology, altered renal Na+,K+-ATPase and renin activity offers further insight into the mechanism underlying the increased blood pressure characteristic of this model.

Figure 1. Stereological analyses of aortic morphology were altered in OHF (filled symbols) compared with OC (open symbols) but not by offspring sex (male and female data are shown separately)

All data are presented as the mean observation from each animal and horizontal lines show group means. A, endothelial cell volume was reduced in OHF animals compared with OC (*P < 0.03); however, there was no sex difference (P < 0.55). B, there was no effect of maternal diet (P < 0.62) nor offspring sex (P < 0.79) on endothelial cell number. C, there was no effect of maternal diet (P < 0.93) nor offspring sex (P < 0.18) on smooth muscle cell volume. D, there was a significant reduction in smooth muscle cell number in OHF animals compared with OC (†P < 0.008); however, there was no effect of offspring sex (P < 0.28). E, there was no effect of maternal diet (P < 0.44) nor sex (P < 0.19) on medial thickness.

Figure 2. Parameters of aortic reactivity were altered in OHF (filled symbols) compared with OC (open symbols) but not by offspring sex (male, circles; female, triangles)

A, passive stiffness (measured in Ca²⁺ free media) was increased in OHF animals compared with OC (*P < 0.04). There was no effect of sex (P < 0.32). Data are shown as means ± s.e.m. (OC male n = 5, OHF male n = 6, OC female n = 8, OHF female n = 5). B, contractile responses to phenylephrine were not altered by maternal diet (P < 0.45) nor by offspring sex (P < 0.83). Data are shown as means ± s.e.m. (OC male n = 6, OHF male n = 6, OC female n = 5, OHF female n = 5). C, endothelium-dependent vasodilatation to ACh was blunted in OHF animals compared with OC (†P < 0.003); however, there was no effect of sex (P < 0.31). Data are shown as mean ± s.e.m. (OC male n = 7, OHF male n = 6, OC female n = 8, OHF female n = 7). D, endothelial independent vasodilatation to aqueous nitric oxide was not altered by maternal diet (P < 0.28) nor by offspring sex (P < 0.37). Data show means ± s.e.m. (OC male n = 6, OHF male n = 5, OC female n = 8, OHF female n = 5).

Figure 3. Stereological analyses of renal morphology were not altered in OHF (filled symbols) compared with OC (open symbols), but there was a significant effect of offspring sex (male, circles; female, triangles)

All data are presented as the mean observation from each animal and horizontal lines show group means. A, there was no effect of maternal diet on glomerular volume (P < 0.12); however, there was a significant effect of offspring sex (*P < 0.001), with males having a greater glomerular volume. B, there was no effect of maternal diet on glomerular number (P < 0.75); however, there was a significant effect of offspring sex (†P < 0.04), with males having more glomeruli than females.

Figure 4. Activities of key renal enzymes were altered by maternal diet (OHF filled bars, OC unfilled bars) and offspring sex, but aldosterone was only affected by offspring sex

A, kidney renin activity was reduced in OHF animals compared with OC (*P < 0.03) and was lower in males compared with females (†P < 0.002). Data represent means ± s.e.m. (OC male n = 9, OHF male n = 9, OC female n = 7, OHF female n = 10). B, plasma aldosterone concentration was not affected by maternal diet (P < 0.26); however, there was a significant reduction in concentration observed in males compared with females (‡P < 0.0001). Data represent means ± s.e.m. (OC male n = 7, OHF male n = 6, OC female n = 6, OHF female n = 5). C, kidney Na⁺,K⁺-ATPase activity was reduced in OHF animals compared with OC (§P < 0.003); however, for this parameter there was no effect of offspring sex (P < 0.33). Data represent means ± s.e.m. (OC male n = 10, OHF male n = 10, OC female n = 10, OHF female n = 11).