Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar-Kyoto rats.
BACKGROUND
Chronic intermittent hypoxia (CIH) is thought to induce several cardiovascular effects in patients with obstructive sleep apnoea (OSA). However, the effects of CIH on patients with long-standing hypertension are unknown.


OBJECTIVE
This prospective study aimed to investigate the influence of combined OSA and hypertension on cardiomyocyte death.


METHODS
Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to repetitive hypoxia-reoxygenation cycles (30 s of 5% O(2); 45 s of 21% O(2)) or room air for 6 h/day during the light phase (10 a.m.-4 p.m.) for 10, 20, or 30 days, and the levels of necrosis and apoptosis induced in their left ventricular cardiomyocyte were examined.


RESULTS
CIH increased the accumulation of reactive oxygen species, which induced cardiomyocyte necrosis in WKY and SHR (both p < 0.05). Cardiomyocyte oxidative stress levels by CIH were higher in SHR than in WKY (p < 0.05); therefore, cardiomyocyte necrosis was amplified (p < 0.05). Notably, if a superoxide-scavenging agent is injected beforehand, cardiomyocyte necrosis can be effectively inhibited (p < 0.05). When WKY and SHR are exposed to CIH, increases in mitochondria-released cytochrome c and activation of caspase-3 are found in the cytosolic fraction only in WKY.


CONCLUSIONS
CIH causes cardiomyocyte loss in SHR mainly through cardiomyocyte necrosis. In WKY however, CIH simultaneously induces apoptosis and necrosis of cardiomyocytes.
Institute of Medical Sciences, College of Medicine, Tzu Chi University, Hualien, Taiwan.
Tsung-I
TI
Chen
Ching-Jung
CJ
Lai
Chien-Ju
CJ
Hsieh
Ke-Li
KL
Tsai
Kun-Ta
KT
Yang
D000818:Animals; D016923:Cell Death / Q000502:physiology*; D006973:Hypertension / Q000473:pathology*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000473:pathology*; D009336:Necrosis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000473:pathology*
D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase