The effects of acute and chronic systemic hypoxia on muscle oxygen supply and oxygen consumption in the rat

Abstract

SUMMARYThe aims of the present study were to evaluate how acute systemic hypoxia affects 0, delivery to skeletal muscle and muscle 0, consumption (voJ of the rat and to establish how these relationships are altered by chronic systemic hypoxia. Thus, the effects of breathing different concentrations of 0, (air, 12 % and 8 % 0,) upon oxygen delivery and vo, were studied in hindlimb muscles of control, normoxic (N) rats and of rats that had been made chronically hypoxic in a chamber at 12 % 0, for 3-4 weeks (CH) rats. Under anaesthesia, arterial blood pressure, femoral blood flow (FBF), arterial 0, content (Ca,02) and venous 0, content in the efflux from hiindlimb were measured. In N rats, changing the inspirate from air to 12 YO and 8 % 0, for 5 min each, reduced C,,,? from 20 f 0.3 ml (100 ml)-' in air to 13 f 1.0 ml (100 ml)-' in 8 % 0,. FBF did not change significantly (1.7 f 0.1 ml m i d in air) so that 0, delivery to hindlimb muscles fell from 0.28 f 0.07 to 0.16 f 0.02 ml min-' in 8 % 0,. Nevertheless, the-??, of hindlimb muscles was well maintained: 0.06 & 0.02 ml min-' in air and 0.08 k 0.02 ml min in 8 % 0,. In CH rats breathing 12 % 0,, Ca,02 (23 f 1.0 ml (100 ml)-') was comparable to that of N rats breathing air, due to an increase in haematocrit, as were FBF (1.6 f 0.2 ml m i d ) and 0, delivery (0.39 f 0.05 ml min-').However, vo2 was 2.5-fold greater in CH rats (0.16 f 0.03 ml min-'). As in N rats, FBF was well maintained at 1.7 f 0.2 and 1.6 f 0.2 ml min-' in 8 % 0, and air, respectively. Further, 3 was also well maintained, at 0.17 f 0.02 and 0.12 f 0.02 ml min-' in 8 % 0, and air, respectively.These results suggest that, contrary to previous reports, muscle vo2 of the rat is independent of 0, delivery over a wide range of 0, delivery values. They also sugges: that muscle Vo, #of CH rats is similarly independent of 0, delivery. The novel finding that muscle Voz has a greater absolute value in CH rats can, we propose, be explained by an increase in voz of the vasculature rather than of the skeletal muscle fibres and reflects increased biosynthetic activity of the vessel walls and/or vascular remodelling. 0 2 .

Obesity induced-insulin resistance causes endothelial dysfunction without reducing the vascular response to hindlimb ischemia

“…3a). This reduction in diameter as well as the reduced capillary density induced by obesity [11-13] might exaggerate the reduced vascular perfusion induced by obesity (reflected by the hypotrophic remodeling, [38]) and impede the ability of the vessels to grow in response to ischemia, mechanism that requires increased vascular conductance and relaxation of the vascular tree [24]. Despite their appearance during the stage of obesity, vascular remodeling and capillary rarefaction appear to have no functional consequence on the ischemic angiogenic response, but may worsen the vascular adaptation to ischemia during the sustained stages of diabetes or contribute to other forms of angiogenesis such as exercise-induced changes in vascularity.…”

Physiological adjustments and arteriolar remodelling within skeletal muscle during acclimation to chronic hypoxia in the rat

“…Blood gas analysis was performed on 130 μl samples by a NovaStat Profile analyser (Stat 3, V. A. Howe, MA, USA), which provided P a,O2 , arterial partial pressure of CO 2 ( P a,CO2 ) and pH, together with haemoglobin O 2 saturation ( S a,O2 ). C a,O2 was then calculated for each sample from the haematocrit and S a,O2 values, as described previously (Marshall & Davies, 1999).…”

“…Mian & Marshall, 1991, 1996), while we have used the hindlimb muscles for many previous studies of gross muscle vascular conductance in systemic hypoxia (e.g. Thomas & Marshall, 1997; Marshall & Davies, 1999).…”

The vascular wall as a regulator of tissue oxygenation

“…Vasoconstriction induced by the administration of noradrenaline and vasopressin significantly increased the amount of oxygen extracted from the perfusate to the isolated hindlimb, kidney, intestine and mesentery of the rat [28]. The oxygen consumption rate was found to increase in rats adapted to chronic systemic hypoxia when they were exposed to the stress of room air [29].…”