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 micrograms/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.
Abernethy
D R
DR
Department of Medicine, Brown University School of Medicine, Providence, R.I., USA.
Laurie
N
N
Andrawis
N S
NS
D000328:Adult; D000803:Angiotensin I / Q000494:pharmacology / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015773:Enalaprilat / Q000494:pharmacology; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000803:Angiotensin I; D012083:Renin; D015773:Enalaprilat