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

1. We have investigated the relationship between O-2 delivery (D-O2) and O-2 consumption (V-O2) 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). 2. In control rats (n = 8), femoral vascular conductance (FVC) increased at each level of hypoxia. Hindlimb D-O2 decreased with the sever it of hypoxia, but muscle V-O2 was maintained until the critical D-O2 value (D-O2,D-erit) was reached at 0.64 +/- 0.06 ml O-2 min(-1) kg(-1); below this V-O2 declined linearly with D-O2. This is a novel finding for the rat but is comparable to the bir,biphasic relationship seen in the dog. 3. In another group of rats (n = 6), (L)-AME caused hindlimb vasoconstriction and attenuated the hypoxia-evoked increases in FVC. D-O2 was so low after (L)-NAME administration that V-O2 was dependent on D-O2 at all levels of hypoxia. 4. In a further group (n = 8), femoral blood flow and D-O2 were restored after (L)-NAME by infusion of the NO donor sodium nitroprusside (20 mug kg(-1) min(-1)). Thereafter, hypoxia-evoked increases in FVC were fully restored. Nevertheless, D-O2,D-erit was increased relative to control (0.96 +/- 0.07 ml O-2 min(-1) kg(-1), P < 0.01). 5. As NOS inhibition limited the ability of muscle to maintain V-O2 during hypoxia, we propose that hypoxia-induced dilatation of terminal arterioles, which improves tissue O-2 distribution, is mediated by NO. However, since the hypoxia-evoked increase in FVC was blocked by L-NAME l,ut restored bp the NO donor, we propose that the dilation of proximal arterioles is dependent on tonic levels of NO, rather than mediated by NO.