LOCAL ANGIOTENSIN-CONVERTING ENZYME-INHIBITION BLUNTS ENDOTHELIN-1-INDUCED INCREASE IN FOREARM VASCULAR-RESISTANCE

Objective: The physiologic role of endothelin-1 is not well established; however, it may have a role in modulation of peripheral vascular tone complimentary to angiotensin II. In vitro and animal studies suggested an interrelationship between angiotensin II and endothelin-1 vasoconstriction. We hypothesized that local vascular or systemic renin-angiotensin II systems must be intact for endothelin-1-mediated vasoconstriction in humans. Methods: To test this hypothesis, responses to brachial artery infusion of endothelin-1 alone and endothelin-1 plus local low-dose infusion of enaliprilat were studied in seven healthy male and seven healthy female volunteers. Results: In these subjects, baseline forearm vascular resistance (mean +/- SEM; 24 +/- 3.5 mm Hg . ml/dl forearm vol/min) increased with a 38.2 ng/min endothelin-1 infusion (61.8 +/- 6.8 mm Hg . ml/dl forearm vol/min; p < 0.01), forearm vascular resistance decreased when 38.2 ng/min endothelin-1 was infused concomitantly with a local 5 mu g/min infusion of enaliprilat (45.5 +/- 5.9 mm Hg . ml/dl forearm vol/min; p < 0.01 compared with endothelin-1 alone). Conclusions: These data indicate that an endothelin-1-induced increase in forearm vascular resistance is inhibited by local forearm angiotensin-converting enzyme inhibition.