Effects of maternal hypoxia on muscle vasodilatation evoked by acute systemic hypoxia in adult rat offspring: changed roles of adenosine and A1 receptors.

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Suboptimal conditions in utero can have long-lasting effects including increased risk of cardiovascular disease in adult life. Such programming effects may be induced by chronic systemic hypoxia in utero (CHU). We have investigated how CHU affects cardiovascular responses evoked by acute systemic hypoxia in adult male offspring, recognising that adenosine contributes to hypoxia-induced muscle vasodilatation and bradycardia by acting on A(1) receptors in normal (N) rats. In the present study, dams were housed in a hypoxic chamber at 12% O(2) for the second half of gestation; offspring were born and reared in air until 9-10 weeks of age. Under anaesthesia, acute systemic hypoxia (breathing 8% O(2) for 5 min) evoked similar biphasic tachycardia/bradycardia, fall in arterial pressure and increase in femoral vascular conductance (FVC) in N and CHU rats (+2.0 vs. +2.7 conductance units respectively). However, in CHU rats, neither the non-selective adenosine receptor antagonist 8-sulphophenyltheopylline (8-SPT), nor the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) affected the increase in FVC, but DPCPX attenuated the hypoxia-induced bradycardia. Further, in N and CHU rats, 5 min infusion of adenosine induced similar increases in FVC; in CHU rats, DPCPX reduced the adenosine-induced increase in FVC (by >50%) and accentuated the concomitant tachycardia. These results suggest that CHU rats have functional A(1) receptors in heart and vasculature, but the release and/or vasodilator influence of adenosine on the endothelium in acute hypoxia is attenuated and replaced by other dilator factors. Such changes from normal endothelial function may have implications for general cardiovascular regulation.


Original languageEnglish
Pages (from-to)5115-25
Number of pages11
JournalThe Journal of Physiology
Issue numberPt 24
Publication statusPublished - 15 Dec 2010

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