Reciprocal changes in adrenal and vascular responsiveness to angiotensin II (Ang II) are part of the normal adaptation to shifts in salt intake. When dietary salt intake is abruptly reduced from high to low, enhancement in aldosterone secretion requires several days to develop. Once established it is not known how quickly the enhancement is reversed with salt repletion. We investigated the time course and relative contributions of salt, volume expansion, or both to this process by studying 15 normotensive subjects; 5 were studied during both high-salt and low-salt balance, and 10 were studied only in low-salt balance. For rapid volume expansion to reverse low-salt balance, 5 subjects received in random order an infusion of normal saline or dextran. The adrenal glomerulosa and renal vascular responses to Ang II were assessed after each volume expansion maneuver. Saline and dextran infusions suppressed plasma renin activity and aldosterone equally, although dextran acted more slowly. Both also increased renal perfusion and renal vascular and pressor responses to Ang II, which in 3 to 7 hours became identical to responses seen during high-salt intake ("modulation"). Saline infusion also blunted adrenal responsiveness to Ang II during that same interval. Despite suppression of the renin-angiotensin system by dextran infusion, aldosterone responsiveness to Ang II remained enhanced. These observations suggest that the renal and vascular responses to Ang II are modulated rapidly by the effects of volume expansion per se.(ABSTRACT TRUNCATED AT 250 WORDS)