Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC123
Sympathetic hyperinnervation induced by chronic hypoxia in utero (CHU) persists into early adulthood
W. Rook1, A. M. Coney1, K. Brain1, J. Marshall1
1. Uni. of Birmingham, Birmingham, United Kingdom.
The link between intrauterine growth restriction (IUGR) and increased risk of adult cardiovascular disease is well established - CHU is a well-known cause of IUGR. In the chronically hypoxic chicken egg, the d19 fetus shows increased sympathetic nerve density and increased noradrenaline content in the femoral artery [1,2] and at 14-15 weeks old an exaggerated sympathetic vasoconstrictor response . However, it is not known if similar hyperinnervation occurs in mammals nor whether it persists into adult life. We have therefore tested these possibilities. After killing by anaesthetic overdose (I.V. sodium pentabarbital 200mg under Halothane anaesthesia, followed by cervical dissertation), tibial arteries (5mm lengths) were taken from age-matched 10-12wk old normal (N) male Wistar rats and compared to those from male offspring of pregnant Wistar dams who were exposed to 12% O2 from day 10-20 of pregnancy (CHU). Each artery was mounted as a stretch preparation and the sympathetic nerve fibres were stained using the glyoxilic acid staining technique . They were then viewed using confocal microscopy and quantitative analysis. Fluorescent area (more than 3SDs above mean background intensity) was higher in CHU than N rats (N: 10.5±0.72% (n=10), CHU: 16.4±1.8% (n=13), P=0.012 Student’s unpaired t-test). Sympathetic nerve density was also markedly higher in CHU (N: 0.75±0.029, CHU: 1.09±0.15, p<0.001,intersects/unit area, Student’s unpaired t-test). Under alfaxalone anaesthesia, N and CHU Rats have similar baseline arterial blood pressure and femoral vascular conductance . In conclusion, CHU-induced hyperinnervation of the tibial artery (that supplies muscles of the rat hindlimb) persists into adulthood. However, this does not appear to have gross systemic cardiovascular consequences at this age. Further work will determine the sensitivity to, and the levels of sympathetic nerve activity present in the muscle vasculature.
Where applicable, experiments conform with Society ethical requirements