Endothelin blockade potentiates endothelial protective effects of ACE inhibitors in saphenous veins.
BACKGROUND
Angiotensin II and endothelin-1 are potent endothelium-derived contracting factors. The effects of acute endothelin antagonism on endothelial function in saphenous vein from patients treated with and without angiotensin-converting enzyme inhibitors were compared.


METHODS
Vascular segments of saphenous vein were obtained perioperatively from 14 patients on angiotensin-converting enzyme inhibitors and 29 controls. In vitro endothelium-dependent and -independent responses to acetylcholine and sodium nitroprusside were assessed by constructing isometric dose-response curves in precontracted rings in the presence and absence of bosentan (endothelinA/B receptor antagonist) and BQ-123 (endothelinA antagonist) using isolated organ baths. Percent maximum relaxation and sensitivity were compared between interventions.


RESULTS
Endothelium-dependent relaxation to acetylcholine was augmented in the angiotensin-converting enzyme inhibitor-treated group (p < 0.005). Both specific and mixed endothelin receptor blockade improved acetylcholine-mediated relaxation in the angiotensin-converting enzyme inhibitor-treated and untreated groups (p < 0.02). The effects of these antagonists were endothelium specific as endothelium-independent responses to sodium nitroprusside remain unaltered.


CONCLUSIONS
These data demonstrate that (1) chronic angiotensin-converting enzyme inhibition improves endothelial function in saphenous veins, and (2) this effect can be further augmented by acute endothelin blockade. These data suggest that antagonism of both angiotensin II and endothelin may be important in attenuating saphenous vein arteriosclerosis.
Ko
Lawrence
L
Division of Cardiac Surgery, The University of Toronto, Toronto General Hospital, Ontario, Canada.
Maitland
Andrew
A
Fedak
Paul W M
PW
Dumont
Aaron S
AS
Badiwala
Mitesh
M
Lovren
Fina
F
Triggle
Christopher R
CR
Anderson
Todd J
TJ
Rao
Vivek
V
Verma
Subodh
S
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000077300:Bosentan; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D013449:Sulfonamides; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D000109:Acetylcholine; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)