Dr. Abernethy et al., LOCAL ANGIOTENSIN-CONVERTING ENZYME-INHIBITION BLUNTS ENDOTHELIN-1-INDUCED INCREASE IN FOREARM VASCULAR-RESISTANCE, Clinical pharmacology and therapeutics, 58(3), 1995, pp. 328-334
Objective: The physiologic role of endothelin-1 is not well establishe
d; however, it may have a role in modulation of peripheral vascular to
ne complimentary to angiotensin II. In vitro and animal studies sugges
ted an interrelationship between angiotensin II and endothelin-1 vasoc
onstriction. We hypothesized that local vascular or systemic renin-ang
iotensin II systems must be intact for endothelin-1-mediated vasoconst
riction in humans. Methods: To test this hypothesis, responses to brac
hial artery infusion of endothelin-1 alone and endothelin-1 plus local
low-dose infusion of enaliprilat were studied in seven healthy male a
nd seven healthy female volunteers. Results: In these subjects, baseli
ne 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 vascula
r resistance decreased when 38.2 ng/min endothelin-1 was infused conco
mitantly 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 al
one). Conclusions: These data indicate that an endothelin-1-induced in
crease in forearm vascular resistance is inhibited by local forearm an
giotensin-converting enzyme inhibition.