Presented at the Neonatal Society 2006 Widdowson Meeting.
Gardner DS1, Symonds ME2
1 Centre for Reproduction and Early Life, Schools of Veter inary Medicine and Science, Sutton Bonington, UK
2 Human Development, University Hospital, University of Nottingham, UK
Introduction: Periconceptional global undernutrition in sheep programs altered cardiovascular control during high circulating levels of angiotensin II in the adult offspring. These effects were apparent despite no change in resting blood pressure. Obesity is known to be deleter ious to cardiovascular control and invariably raises resting blood pressure. We hypothesised that juvenile obesity in sheep would exacerbate cardiovascular anomalies in prenatally nutritionally challenged sheep by one year of age, and that the effect was largely through altered sympathetic activity.
Methods: 29 twin-bearing ewes received a control (C, 7 MJ/day; n=16) or nutrient restricted diet (NR, 50% C intake ~3.5 MJ/day; n=13) from day 30 to 80 days and control diet thereafter (12-13 MJ/day near term). Lambs were ewe reared as singletons (one twin being humanely put down) and then subjected to a low activity, increased food availability environment to promote fat deposition (Obese controls OC, n=8; Obese nutrient restricted ONR, n=13) or pasture grazed with high activity and equivalent food availability; Lean controls LC, n=8). At one year of age the lambs were surgically instrumented under 1-2% isoflurane (75:25 O2/N2O) with carotid and jugular cannulae. After at least 2 days recovery, and on 3 separate days after a 30min resting period angiotensin II was infused in stepwise increments every 10 mins from 0-60 μg.kg-1.min-1with/without 1) saline, 2) atropine (2.4mgs bolus with 0.6mg.h-1 infusion) or 3) propranolol (20mgs I.V. bolus with 30 mg.h-1 infusion). Cardiovascular data from pressure transducers (SensorNor 840; S 4925) were logged each second by a data acquisition system (Po-Ne-Mah; Version 3, Gould Instrument Systems Inc). Data are given as Means ± S.E.M. and were analysed by two-way ANOVA using SPSS v14. Not all data were available for all studies.
Results: Resting systolic blood pressure was signif icantly higher in obese vs. Lean sheep (oc, 116±2; onr, 119±3 vs. Lc 105±2 mmhg) with no interaction between group *treatment. All sheep responded to an angiotensin II infusion with an increase in arterial pressure (~65 mmHg) that was similar between groups. Pre-treatment with atropine had no effect on the change in pressure with angiotensin II but pre-treatment with propranolol significantly (p<0.05) attenuated the increase in systolic pressure in onr only (figure 1).
Conclusions: Sheep that have become obese through reduced physical activity and a modest increase in food intake through adolescence have hypertension as young adults. Nevertheless the hypertensive sheep respond to a cardiopressor challenge appropriately. However, when extrinsic beta-adrenergic, but not parasympathetic, support to the heart is blocked, then the increment in pressure is significantly attenuated in only those sheep exposed to maternal nutrient restriction in early-mid gestation. The data indicate altered beta-adrenergic activity in prenatally nutrient restricted sheep.
Acknowledgements: Supported by the British Heart Foundation.