Intermittent hypoxia improves atrial tolerance to subsequent anoxia and reduces stress protein expression

Abstract

We tested the hypothesis that 21 days of intermittent hypoxia (IH) increases the tolerance of the spontaneously beating guinea-pig double atria preparation to acute in-vitro hypoxia, and reduces cardiac stress protein expression. A total of 28 guinea-pigs were divided into four groups: (i) IH; (ii) IH + in-vitro hypoxia (IH + IV); (iii) control (CON); (iv) control + in-vitro hypoxia (CON + IV). The IH animals were exposed to 8% O2/0.3% CO2 for 12 h day-1 for 21 days. Normoxic controls were exposed to room air for the same duration. Acute in-vitro hypoxia (20, 10, 5 and 0% O2 in 5% CO2) was introduced into the atrial preparation. Heat shock protein (Hsp) 70 and Hsp90 content were determined by Western blotting. Intermittent hypoxia groups demonstrated typical responses to chronic hypoxic exposure, characterized by significantly (P < 0.05) lower body weights, reduced growth rates and increased heart weight/body weight ratios. In the CON + IV group, in-vitro hypoxia reduced heart rate (20% O2, -30 +/- 8 beats min (-1); 10% O2, -34 +/- 8 beats min (-1); 5% O2, -37 +/- 9 beats min (-1) and 0% O2, -51 +/- 9* beats min (-1): *P < 0.05 vs. 20% O2). At 0% O2, the decrease in the rate response was significantly attenuated in the IH + IV (-30 +/- 8 beats min (-1); n=10) compared with the CON + IV (-51 +/- 9 beats min (-1); n=10). IH significantly reduced atrial Hsp70 and Hsp90 expression, however, levels of both proteins were unchanged in the ventricle. Furthermore, Hsp90 and to a lesser degree Hsp70 in the atria remained suppressed following in-vitro hypoxia in the IH group. Our results show that the increased resistance of the isolated atria to anoxia following IH may contribute to the concomitant reductions in basal and hypoxia-induced Hsp expression as the overall stress response is reduced.

Preinduction of HSP70 promotes hypoxic tolerance and facilitates acclimatization to acute hypobaric hypoxia in mouse brain

“…Under hypoxia stress, cells transactivate a variety of genes in order to adapt to altered metabolic status or, alternatively, to induce irreversible cell toxicity. It was previously reported that HSP70 serves as a key modulator of cellular responses to hypoxia (Mohan et al 2001;Rafiee et al 2003;Guanghe and Feng 2007), and hypoxia-induced HSP70 expression suggests a positive correlation between stress protein expression and protection against myocardial damage (Dillmann and Mestril 1995).…”

Glucoregulatory Consequences and Cardiorespiratory Parameters in Rats Exposed to Chronic–Intermittent Hypoxia: Effects of the Duration of Exposure and Losartan

“…Some studies in rodents also reported less dramatic changes in baseline cardiovascular and cognitive parameters (Greenberg et al, 1999; Kraiczi et al, 1999; Reeves et al, 2003; Naghshin et al, 2009; Knight et al, 2011), but it is not clear whether the lesser magnitude of the effects was related to less severe hypoxia (nadirs of 6–10%) or other factors. It is also of note that numerous studies report a positive effect of CIH on endurance, resistance to ischemic injury, glucose disposal, and hypertension (Mohan et al, 2001; Cai et al, 2003; Chiu et al, 2004; Serebrovskaya et al, 2008; Lyamina et al, 2011; Tonini et al, 2011), but the CIH protocols used to achieve these beneficial effects often involve less frequent cycling and less severe hypoxia than those used in studies that aim to model the periodic O 2 desaturations that occur in OSA patients.…”

Hypoxia Modulates Expression of the 70-kD Heat Shock Protein and Reduces <i>Leishmania</i> Infection in Macrophages

“…Interestingly, hypoxia reduces the expression of HSP70 in human endothelial cells and atrial tissue [25,27]. In the only study performed with macrophages, low levels of HSP70 were observed in cells exposed to a single period of hypoxia when compared with cells subjected to repeated cycles of hypoxia/reoxygenation [38].…”