Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension

Abstract

Maduwegedera D, Kett MM, Flower RL, Lambert GW, Bertram JF, Wintour EM, Denton KM. Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension. Am J Physiol Regul Integr Comp Physiol 292: R706 -R714, 2007. First published November 9, 2006; doi:10.1152/ajpregu.00458.2006.-Previously, we demonstrated that adult blood pressure was increased in offspring of rabbit mothers with chronic secondary renal hypertension. Our study identified sex-specific differences in the programming of hypertension, with female, not male, offspring, having increased blood pressure at 30 wk of age. The aim of this study was to characterize the maternal hypertension during pregnancy to determine potential programming stimuli. Further, we examined the impact of chronic maternal hypertension on offspring birth weight, nephron number, and renal noradrenaline content (as an index of renal innervation density). Three groups of mothers and their offspring were studied: two-kidney, one-wrap (2K-1W, n ϭ 9 mothers) hypertensive, two-kidney, two-wrap (2K-2W, n ϭ 8) hypertensive, and a sham-operated group (n ϭ 9). Mean arterial blood pressure was increased by ϳ20 mmHg throughout pregnancy in both hypertensive groups compared with sham mothers (P G Ͻ 0.001). Plasma renin activity (PRA; PG Ͻ 0.05) and aldosterone (PG Ͻ 0.05) levels were increased during gestation in the 2K-1W, but not the 2K-2W mothers. Birth weight was increased by ϳ20% in offspring of both groups of hypertensive mothers (PT Ͻ 0.001), though this was associated with a reduction in litter size. Renal noradrenaline content was increased (ϳ40%, P Ͻ 0.05) at 5 wk of age in female 2K-1W offspring compared with sham offspring. Glomerular number was not reduced in female offspring of either group of hypertensive mothers; however, glomerular tuft volume was reduced in female 2K-2W offspring (P Ͻ 0.05), indicative of a reduction in glomerular filtration surface area. In conclusion, the two models of renal hypertension produced differential effects on the offspring. The impact of a stimulated maternal renin-angiotensin system in the 2K-1W model of hypertension may influence development of the renal sympathetic nerves and contribute to programming of adult hypertension. fetal programming; kidney; renal innervation; glomerular number; renal hypertension CHRONIC HYPERTENSION DURING pregnancy is an increasing problem as women are tending to have children later in life when the incidence of obesity, diabetes, and renal disease associated hypertension is increased. The babies of women with chronic hypertension not only have acute problems perinatally, but more disturbingly, may have an increased long-term burden in the form of future cardiovascular risk (22, 53). There is now compelling evidence, both epidemiological and experimental, to support the hypothesis that events occurring in fetal life can have life-long consequences for the health of the adult (3, 24). The importance of this issue has been recently highlighted in a National...

A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats

“…It has been found that estradiol inhibits and androgen promotes the progression of renal injury (3,16,39,48) and that in females NO release is greater (51). In multiple studies of developmental plasticity, in different species including humans, sex differences have been observed (1,17,25,28). We also observed sex differences after perinatal molsidomine in FHH, possibly indicating interaction between steroid-dependent or Y-chromosome genes and the RF loci.…”

Developmental programming of a reduced nephron endowment: more than just a baby's birth weight

“…Furthermore, a reduced nephron number has been documented in the absence of hypertension (29,51,112) with or without changes in birth weight. Conversely, programmed hypertension has been demonstrated in the absence of changes in birth weight or decreased nephron number in a number of animal models, including maternal overfeeding, maternal hypertension, and maternal water restriction (16,25,70,72), demonstrating that hypertension can also be programmed independently of a reduction in nephron number. Previously, we suggested potential mechanisms whereby this may occur, including alteration in the renin-angiotensin system, renal sympathetic innervation, and tubular transport mechanisms in the kidney (26).…”

Chronic maternal hypertension affects placental gene expression and differentiation in rabbits

“…Experiments were performed at three timepoints across gestation, gestational age day 14 (GA14), gestational age day 21 (GA21) and gestational age day 28 (GA28) (term, 32 days) in three groups of rabbits: 2K-1W, 2K-2W and sham-operated animals (number of mothers and associated placentas per group shown in Table 1), prepared as previously described [13,14,25,26]. The animals were allowed 4 weeks' recovery during which time hypertension developed.…”

“…Preterm birth and being small for gestational age are associated with increased arterial pressure in early childhood and adult life [11,12]. We have previously shown that offspring from rabbit mothers with mild preexisting hypertension have elevated arterial pressure as adults [13], which was associated with altered renal innervation but without accompanying changes in birthweight or nephron number [14].…”