Pre-weaning Growth Hormone Treatment Reverses Hypertension, Endothelial Dysfunction and Alters Heart Development in Adult Male Offspring Induced as a Consequence of Maternal Undernutrition

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 498-514-Female Reproductive Endocrinology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-512
Clint Gray*, Minglan Li, Clare Marie Reynolds and Mark Hedley Vickers
University of Auckland, Auckland, New Zealand
Maternal undernutrition is known to cause cardiac hypertrophy, elevated blood pressure (BP) and endothelial dysfunction in adult offspring. Few studies have investigated interventions during the early life period of developmental plasticity to ameliorate programming of cardiac hypertrophy, hypertension and vascular disorders. We utilised a model of maternal undernutrition to examine the effects of neonatal growth hormone (GH) treatment on BP and vascular function in adulthood. Female Sprague-Dawley rats were fed either a standard control diet (CON) or 50% of CON intake throughout pregnancy (UN). From neonatal day 3 until weaning (day 21), CON and UN pups received either saline (CON-S, UN-S) or GH (2.5ug/g/day)(CON-GH, UN-GH). All dams were fed ad libitum throughout lactation. Male offspring were fed a standard diet until the end of the study. Systolic BP (SBP) was measured at day 150 by tail cuff plethysmography. At day 160, intact mesenteric vessels were mounted on a pressure myograph. Responses to pressure, agonist-induced constriction and endothelium-dependant vasodilators were investigated to determine vascular function. Despite no change in blood pressure, SBP was increased in UN-S groups and normalised in UN-GH groups (CON-S 121±2mmHg, CON-GH 115±3, UN-S 146±3, UN-GH 127±2). Pressure mediated dilation was reduced in UN-S offspring and normalised in UN-GH groups. Vessels from UN-S offspring demonstrated a reduced constrictor response to phenylephrine and reduced vasodilator response to acetylcholine. Furthermore, preliminary histological investigation of heart development and structure revealed larger hearts in the UN-S offspring, with a beneficial remodelling of heart structure in UN-GH offspring hearts. In conclusion, pre-weaning GH treatment reverses the negative effects of maternal UN on SBP and vasomotor function in adult offspring. These changes were paralleled by an altered cardiac structural change, indicative of GH-induced remodelling. These data suggest that developmental cardiovascular programming is potentially reversible by early life GH treatment and that GH can reverse the cardiac and vascular adaptations resulting from early life undernutrition.

Nothing to Disclose: CG, ML, CMR, MHV

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Sources of Research Support: Gravida: National Centre for Growth and Development