1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval-cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min. 2. Caval-cuff inflations were performed after 10 min exposure to 100, 21, 12–14 and 8–10% O
2, with and without the addition of 3–4% CO
2, in randomized order. 3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased. 4. During Phase I, there were independent linear relationships between
Pao
2 (but not
Pao
2) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of
Pao
2, the greater was the rate of fall of SVCI and the less the rate of fall of MAP. 5. There was an inverted U-shaped effect of
Pao
2, on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O
2), Phase II occurred later than during normoxia (21% O
2); and (b) across the normoxic and hypoxic gas mixtures (21–8% O
2, with and without added CO
2), there was an independent linear relationship between
Pao
2 (but not
Pao
2 or
Pao
2×
Pao
2) and the level of CI at which Phase II occurred. That is, the lower the level of
Pao
2, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia.
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