Effect of intermittent hypoxia on cardiovascular function, adrenoceptors and muscarinic receptors in Wistar rats

Abstract

The usual model of intermittent hypoxia (sleep apnoea) corresponds to repeated episodes of hypoxia from a few seconds to a few hours interspersed with episodes of normoxia. The aim of this study was to evaluate in rats the effect of two periods of intermittent exposure for 2 months to hypoxia (IHX1,24 h in hypoxia (428 Torr), 24 h in normoxia; IHX2,48 h in hypoxia (428 Torr), 24 h in normoxia) as a new model of hypoxia simulating intermittent exposure to high altitude experienced by Andean miners. We assessed the haematological parameters, time course of resting heart rate and systolic blood pressure. We also evaluated the expression of adrenergic and muscarinic receptors. IHXl and IHX2 produced an increase in haematocrit, haemoglobin concentration and mean corpuscular volume as previously seen in most hypoxic models. IHXl and IHX2 induced a simiiar sustained elevation of systolic blood pressure (132 k 2 and 135 f 3 mmHg, respectively, vs. the control level of 121 & 16 mmHg) after I0 days of exposure without change in heart rate. Right ventricular (RV) hypertrophy (225 f 13 and 268 k 15 mg g-I, vs. 178 k 7 mg g-') and downregulation of a,-adrenoceptor (RV 127 k 21 and 94 k 16 fmol mg-' vs. 157 f 8 fmol mg-'; left ventricle (LV): 141 f 5 and 126 f 9 fmol mg-' vs. 152 f 5 fmol mg-') have been found in both groups, with right ventricular hypertrophy being greater and a,-adrenoceptor density being lower in IHX2 than in HX1 groups. These data indicate that both parameters are related to the time of exposure to hypoxia. IHXl and IHXZ produced the same magnitude of upregulation of muscarinic receptors (LV, 60%; RV, 40%), and no change in /3-adrenoceptors. In conclusion, exposure to intermittent hypoxia led to polycythaemia and RV hypertrophy as observed in other types of hypoxia. A specific cardiovascular response was seen, that is an increase in blood pressure without change in heart rate, which was different from the one observed in episodic and chronic hypoxia. Furthermore, this model involved specific modifications of a,-adrenergic and muscarinic expression. Expen 'mental Physiologv (2002) 87.4,453-460.

Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice

“…Less reproducible findings have been reported for HR changes following CIH. Indeed, both significant increases or no changes of the HR in rats and mice have been described after intermittent hypoxia or sleep apnea (7,17). Tachycardia is a frequent finding in OSA patients (38).…”

Time Course of Endocrine Changes in the Hypophysis-Gonad Axis Induced by Hypobaric Hypoxia in Male Rats

“…Male rats have previously been demonstrated to respond to CHH with cardiovascular changes similar to mine workers labouring at high altitude [1]. Exposure of male rats to intermittent hypobaric hypoxia and chronic hypobaric hypoxia produces an increase in haematocrit, decrease in testicular mass, deterioration of interstitial cells, increase of the interstitial space, damage to the germinal epithelium, increase of the seminiferous tubule lumen, a strong metabolic stress and loss of spermatogenic cells [8,9].…”

“…This also implies that it is highly likely that the plasma volume would be decreased and that all blood cellular components and protein or protein bound metabolites would be concentrated in rats exposed to CHH. Although part of the increase in haematocrit could be attributed to a decrease in the plasma volume (7-8%), the changes in haematocrit observed previously [1,8,9] should be ascribed to an increase in the number of red blood cell, most likely due to erythropoietin activation of bone marrow in CHH rats (e.g., [14]). The proposed decrease in plasma volume implies that decreases of plasma components would be underestimated, while increases in plasma components could be partly attributed to blood concentration.…”

“…Dev. 54: [18][19][20][21] 2008) hronic hypobaric hypoxia (CHH) is experienced by an increasing number of sea level natives exposed to high altitude because of tourism, border patrol, mining or rural health and education activities [1]. It has been suggested that hypobaric hypoxia reduces fertility in humans.…”

Melatonin Protects the Heart, Lungs and Kidneys from Oxidative Stress under Intermittent Hypobaric Hypoxia in Rats

“…It is estimated that there is a working population of over 55,000 who are exposed to hypobaric hypoxia (high altitude sickness). Miners work under these conditions for 4 to 20 days, followed by days off at sea level, and this is repeated over several years (Jalil et al, 1994, Germack et al, 2002Richalet et al, 2002). Intermittent exposure to high altitudes is virtually unknown to date; however it is an unusual condition for workers involving a series of changes at the physiological and cellular levels aimed to compensate the decrease in partial oxygen pressure (PO 2 ).…”