Vasodilatation, oxygen delivery and oxygen consumption in rat hindlimb during systemic hypoxia: roles of nitric oxide

Abstract

We have investigated the relationship between O2 delivery (DO2) and O2 consumption (VO2) in hindlimb muscle of anaesthetised rats during progressive systemic hypoxia. Since muscle vasodilatation that occurs during hypoxia is nitric oxide (NO) dependent, we examined the effects of the NO synthase (NOS) inhibitor nitro‐l‐arginine methyl ester (l‐NAME). In control rats (n= 8), femoral vascular conductance (FVC) increased at each level of hypoxia. Hindlimb DO2 decreased with the severity of hypoxia, but muscle VO2 was maintained until the critical DO2 value (DO2,crit) was reached at 0.64 ± 0.06 ml O2 min−1 kg−1; below this VO2 declined linearly with DO2. This is a novel finding for the rat but is comparable to the biphasic relationship seen in the dog. In another group of rats (n= 6), l‐NAME caused hindlimb vasoconstriction and attenuated the hypoxia‐evoked increases in FVC. DO2 was so low after l‐NAME administration that VO2 was dependent on DO2 at all levels of hypoxia. In a further group (n= 8), femoral blood flow and DO2 were restored after l‐NAME by infusion of the NO donor sodium nitroprusside (20 μg kg−1 min−1. Thereafter, hypoxia‐evoked increases in FVC were fully restored. Nevertheless, DO2,crit was increased relative to control (0.96 ± 0.07 ml O2 min−1 kg−1, P < 0.01). As NOS inhibition limited the ability of muscle to maintain VO2 during hypoxia, we propose that hypoxia‐induced dilatation of terminal arterioles, which improves tissue O2 distribution, is mediated by NO. However, since the hypoxia‐evoked increase in FVC was blocked by l‐NAME but restored by the NO donor, we propose that the dilatation of proximal arterioles is dependent on tonic levels of NO, rather than mediated by NO.

Factors that render the kidney susceptible to tissue hypoxia in hypoxemia

“…In this respect, the kidney appears no different from the hindlimb vascular bed in which V O 2 was also maintained in the face of moderate hypoxemia, as has been demonstrated previously (9,10). For the kidney, the adaptive feature of this phenomenon is that it allows renal tubular function to operate normally under hypoxic conditions.…”

“…Analogous experiments were performed in the hindlimb to assess how responses of kidney oxygenation to hypoxemia differ from those of skeletal muscle. No attempt was made to denervate the hindlimb, since hypoxemia does not lead to sympathetically mediated vasoconstriction in this vascular bed but rather vasodilatation dependent on local factors such as adenosine and nitric oxide (9,10).…”

Short-term hypoxic vasodilationin vivois mediated by bioactive nitric oxide metabolites, rather than free nitric oxide derived from haemoglobin-mediated nitrite reduction

“…Hypoxia-induced vasorelaxation may be reversed by scavenging NO (Pohl & Busse, 1989), or inhibiting sGC with methylene blue (Iwamoto et al, 1992). Whereas increased NO synthesis by NOS may be a potential cause of hypoxic vasodilation (Edmunds & Marshall, 2001;Hunter et al, 2003), others report an ineffectiveness of NOS inhibition on decreased hind limb resistance (Vallet et al, 1994) and dilation of small coronary arteries (Liu & Flavahan, 1997) induced by hypoxia.…”

Intermittent pneumatic leg compressions acutely upregulate VEGF and MCP-1 expression in skeletal muscle

“…Oxygen uptake (V O2) was calculated as the product of FBF and the systemic arterial-venous (a-v) O 2 difference and expressed relative to body weight (14).…”