EFFECTS OF ANGIOTENSIN-II INFUSION AT PRESSOR AND SUBPRESSOR DOSES ONENDOTHELIN-1 PLASMA-LEVELS IN HEALTHY-MEN

Several lines of evidence suggest that effects of angiotensin-II (A-II ) could be mediated in part by endothelin-1 (ET-1): A-II enhances prod uction and secretion of ET-1 which in turn may contribute to the press er effects and mitogenic actions of A-II. We have conducted a randomiz ed controlled cross-over study to investigate whether A-II increases E T-1 plasma levels in humans at presser doses. Each of the eight health y male volunteers received a subpressor and presser dose of A-II which were assessed by titration of the individual dose dependent blood pre ssure responses to A-II-infusion The mean subpressor dose of A-II was 0.62 ng/kg/min. (range: 0.31-1.25); the mean presser dose of A-II was 8.44 ng/kg/min. (range 2.5-20), yielding an average increase in mean a rterial pressure by 35% (95% confidence interval [CI]: 24-45%). Plasma ET-1 concentrations increased significantly only in response to press er doses of A-II (Friedman ANOVA p=0.022): ET-1 increased by 89 % (CI: 24-154%) over baseline (1.7 pmol/L; CI: 1.4-2.0) 60 min. after starti ng the presser infusion of A-II and remained elevated throughout the 4 -hours observation period. In conclusion, A-II at presser doses but no t at subpressor doses induced an increase in plasma levels of ET-1 in healthy subjects. This finding may be of relevance for various disease s associated with increased production of A-II and could potentially h ave therapeutic implications.