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Ann Thorac Surg 2002;73:1185-1188
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Endothelin blockade potentiates endothelial protective effects of ace inhibitors in saphenous veins

^a Division of Cardiac Surgery, The University of Toronto, Toronto General Hospital, Toronto, Ontario, and Division of Cardiac Surgery, The University of Calgary, Calgary, Alberta, Canada

* Address reprint requests to Dr Verma, Division of Cardiac Surgery, The University of Toronto, Toronto General Hospital, 200 Elizabeth St, 14th Floor, Eaton Wing EN 14-217, Toronto, ON M5G 2C4, Canada
e-mail: subodh.verma{at}sympatico.ca

Presented at the Poster Session of the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.

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 (endothelin_A/B receptor antagonist) and BQ-123 (endothelin_A 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.

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