Acute hypoxaemia increases cortisol and catecholamine plasma concentration in fetal sheep. Chronic hypoxia of pregnancy at high altitude blunts fetal cortisol response to an ACTH challenge (Harvey LM et al. 1993) and increases the noradrenergic contribution compared to lowland fetal sheep. However, it is unknown the effect of chronic hypoxaemia of pregnancy on these responses in highland newborn lambs. The aim of this study was to determine ACTH, cortisol and catecholamine plasma concentration during basal and acute hypoxaemic conditions in lambs which have undergone gestation at high and at low altitude. Under general anesthesia (ketamine 10 mg/kg i.m.), 5 lambs born at low altitude (8±1 days old; 6±1 kg, 580 m ; LA) and 6 at high altitude (12±2 days old; 5±1 kg 3,580 m; HA), were chronically catheterized with femoral vascular catheters. Three days after surgery, the lambs were submitted to experiments based on a 3h protocol: 1h basal (B), 1h of acute hypoxemia (H; PaO2 32±1 mmHg) and 1h of recovery (R). Blood samples were obtained to measure pH, PO2, PCO2 values and ACTH, cortisol (RIA), and catecholamines plasma concentrations (HPLC). Data are expressed as means±SEM and differences were tested using two way ANOVA for repeated measures followed by the Newman-Keuls test (*P<0.05). The results showed that HA lambs have a marked decrease in plasma cortisol (ng ml-1) basally and during acute hypoxemia (B 18±3*; H 32±8*; R 24±7) compared to LA (B 64±12; H 107±36; R 29±7). Furthermore, there was a lack of correlation between ACTH and cortisol plasma concentrations in HA, correlation that was significant in LA. Noradrenaline (pg ml-1) showed a substantial increase in HA (B 2849±499*; H 4926±1270*; R 4334±1091*) compared to LA (B 801±80; H 1176±407; R 953±172). In contrast, plasma adrenaline did not show any differences between HA and LA These data suggest that chronic hypoxaemia during fetal and neonatal life blunts adrenocortical response in highland lambs. Moreover, the pronounced stimulation of the noradrenergic system observed in chronic hypoxaemia not only in fetal but also in postnatal life may have consequences for cardiovascular health in later life. All animal procedures approved by the Ethical Committee, Faculty of Medicine, University of Chile.
King's College London (2005) J Physiol 565P, PC177
Communications: ADRENOCORTICOMEDULLAR RESPONSE TO ACUTE HYPOXEMIA IN CHRONIC HYPOXEMIC NEWBORN LAMBS
Riquelme, R A; Herrera, E A; Sanhueza, E A; Pulgar, V M; Reyes, V R; Parer, J T; Giussani, D A; Blanco, C E; Hanson, M A; Llanos, A J;
1. Bioquimica y B Mol, Fac Cs Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile. 2. Programa de Fisiopatologia, ICBM,Fac Medicina, Universidad de Chile, Santiago, Chile. 3. U California San Francisco, San Fco, CA, USA. 4. U Cambridge, Cambridge, United Kingdom. 5. U Maastricht, Maastricht, Netherlands. 6. U Southampton, Southampton, United Kingdom. 7. INCAS, Universidad de Chile, Santiago, Chile.
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Where applicable, experiments conform with Society ethical requirements.