1. The effects of acute volume expansion on vascular resistance and reactivity to noradrenaline and angiotensin II are reported in this study. The estimated circulating blood volume of pentobartibal-anaesthetized dogs was expanded by about 35% with equilibrated donor blood. The animals were bilaterally nephrectomized to sustain expanded volume.

2. Functional changes in vascular smooth muscle were determined in the flow controlled, vascularly isolated, denervated, perfused hind limb preparation in the same animal.

3. Systemic volume expansion per se had no immediate influence on vascular resistance. However, resistance in the hind limb, as determined by the shift of the pressure-flow curves, progressively increased 60 and 120 min after volume expansion. The changes noted after 120 min were significantly greater than those observed after 60 min.

4. The changes in vascular resistance were accompanied by potentiation of the vascular responses to noradrenaline but not to angiotensin II. Significant shifts which occurred in the noradrenaline dose-response curves were similar to those of the resistance curves.

5. in closely simulated control experiments in dogs whose kidneys were intact or had been removed, and whose blood had or had not been equilibrated with donor blood, the above-mentioned vascular changes were not observed in the absence of volume expansion.

6. It is suggested that the functional changes observed in the hind limb vasculature after volume expansion are related to the presence of a circulating substance. From the data obtained from the experimental model used in this study, it can be concluded that such a substance is not released from the kidney.

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