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Sex Differences in Renal and Cardiovascular Function: Physiology and Pathophysiology

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

¹Department of Physiology Monash University, ²Baker Heart Institute and ³Department of Anatomy and Cell Biology Monash University, Melbourne, Australia

Submitted 3 July 2006 ; accepted in final form 24 October 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 = 9 mothers) hypertensive, two-kidney, two-wrap (2K-2W, n = 8) hypertensive, and a sham-operated group (n = 9). Mean arterial blood pressure was increased by 20 mmHg throughout pregnancy in both hypertensive groups compared with sham mothers (P_G < 0.001). Plasma renin activity (PRA; P_G < 0.05) and aldosterone (P_G < 0.05) levels were increased during gestation in the 2K-1W, but not the 2K-2W mothers. Birth weight was increased by 20% in offspring of both groups of hypertensive mothers (P_T < 0.001), though this was associated with a reduction in litter size. Renal noradrenaline content was increased (40%, P < 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 < 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

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