Hypoxia of sleep apnoea: cardiopulmonary and cerebral changes after intermittent hypoxia in rats.
Sleep apnoea (SA) is common, especially in elderly people. In severe cases, arterial P(O2) may be lowered for a third or more in a night of sleep. To simulate the degree and duration of severe SA we exposed rats in a normobaric environmental chamber to 10% O(2) for 4h daily for 56 days (intermittent hypoxia: IH group) and compared them with rats continuously exposed for 8 weeks (continuous hypoxia: CH group) and control rats breathing room air (normoxic: N group). We found significant cardiopulmonary and cerebral changes. Right ventricular hypertrophy developed in IH and to a greater extent in CH. Small peripheral lung vessels developed thicker walls (assessed by a new method), which reduced their lumen, more in CH than IH. Coronal brain sections were immunostained for the glucose-transporter 1 (GLUT1) and the vascular endothelial growth factor (VEGF). The percentages of immunoreactivity in the frontal and temporal cortex, hippocampus, accumbens and putamen were determined by image-capture analysis. We noted GLUT1 immunoreactivity of the capillaries was similarly increased in all regions after CH but less so after IH. However, there was a significant linear trend in GLUT1 reactivity from N to IH to CH (R(2) = 0.73, P = 0.007) that was also confirmed by analysis of variance. The extent of VEGF-stained neurones and glial cells was significantly increased in all regions after IH but not after CH. This suggests that the signals for angiogenesis were complete or arrested after CH. Our findings have implications for the elderly subjected to hypoxic episodes during sleep apnoea.
Kalaria
Raj N
RN
Wolfson Centre, Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK.
Spoors
Louise
L
Laude
Elizabeth A
EA
Emery
Celia J
CJ
Thwaites-Bee
Denise
D
Fairlie
John
J
Oakley
Arthur E
AE
Barer
David H
DH
Barer
Gwenda R
GR
D000222:Adaptation, Physiological; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D051272:Glucose Transporter Type 1; D006984:Hypertrophy / Q000209:etiology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000473:pathology*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000473:pathology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012891:Sleep Apnea Syndromes / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D042461:Vascular Endothelial Growth Factor A