1. To study which factors determine the balance between the antagonistic and agonistic effects of the angiotensin II analogue [Sar1,Ala8]angiotensin II (saralasin) in man, saralasin was infused in subjects on a ‘normal’ sodium intake (group 1) and during sodium restriction with appropriately elevated plasma angiotensin II levels (group 2), and in sodium-restricted subjects in whom plasma angiotensin II was suppressed by converting-enzyme inhibition with captopril (group 3).
2. The saralasin-induced increase of plasma aldosterone concentration in group 1 was different (P<0.005) from the decrease in group 2, whereas saralasin produced a significant increase of plasma aldosterone in group 3. For the three groups combined the changes of plasma aldosterone were significantly related to control angiotensin II levels, but not to the 24 h urinary sodium excretion. The data suggest that it is the rise of angiotensin II in response to the sodium restriction and not the sodium restriction per se that is associated with the antagonistic action of saralasin on the adrenal receptors.
3. On average mean intra-arterial pressure at 30 min was not affected by saralasin in group 1, had decreased in group 2 and increased (P<0.001) by 4.4 mmHg in group 3. Overall the changes of arterial pressure were significantly related to control angiotensin II, but not to the 24 h sodium excretion, suggesting that the angiotensin II levels predominantly determine the agonistic-antagonistic balance of saralasin's actions on arterial pressure.
4. Although saralasin did not affect plasma renin activity in group 1, plasma renin rose in group 2 and was reduced by 40% (P<0.001) in group 3. For the three groups together the changes of plasma renin activity were significantly related to the changes of mean arterial pressure both on single and multiple regression analyses. The changes of pressure ‘explain’, however, only a fraction of the changes of plasma renin; it is suggested that saralasin has an agonistic effect on the renal receptors involved in the direct suppression of renin by angiotensin II in low-sodium, low-angiotensin conditions and that an antagonistic effect may contribute to the saralasin-induced rise of renin during sodium restriction with appropriate angiotensin II levels.
