Effects of angiotensin-II infusion at pressor and subpressor doses on endothelin-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 production and secretion of ET-1 which in turn may contribute to the pressor effects and mitogenic actions of A-II. We have conducted a randomized controlled cross-over study to investigate whether A-II increases ET-1 plasma levels in humans at pressor doses. Each of the eight healthy male volunteers received a subpressor and pressor dose of A-II which were assessed by titration of the individual dose dependent blood pressure 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 pressor dose of A-II was 8.44 ng/kg/min. (range 2.5-20), yielding an average increase in mean arterial pressure by 35% (95% confidence interval [CI]: 24-45%). Plasma ET-1 concentrations increased significantly only in response to pressor 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 starting the pressor infusion of A-II and remained elevated throughout the 4-hours observation period. In conclusion, A-II at pressor doses but not at subpressor doses induced an increase in plasma levels of ET- 1 in healthy subjects. This finding may be of relevance for various diseases associated with increased production of A-II and could potentially have therapeutic implications.

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