HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Guo-Wei He Anthony Furnary Anthony P.C. Yim Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by He, G.-W. Articles by Yim, A. P.C. Search for Related Content PubMed PubMed Citation Articles by He, G.-W. Articles by Yim, A. P.C. Related Collections Coronary disease

---

Original Articles: Cardiovascular

Role of Endothelin-1 Receptor Antagonists in Vasoconstriction Mediated by Endothelin and Other Vasoconstrictors in Human Internal Mammary Artery

^a Providence Heart and Vascular Institute, Albert Starr Academic Center, Portland, Oregon
^b Department of Surgery, Oregon Health and Science University, Portland, Oregon
^c Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR
^d Wuhan Heart Institute, The Central Hospital of Wuhan, Wuhan, China

Accepted for publication May 29, 2007.

^_* Address correspondence to Prof He, Department of Surgery, Block B, 5A, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. (Email: gwhe{at}cuhk.edu.hk).

Background: The action of antagonists for endothelin type A (ET_A) and type B (ET_B) on the vasoconstriction mediated by various vasoconstrictors in the human bypass grafts have not been well-defined. We studied the role of antagonists for both ET_A and ET_B receptors in vasoconstriction mediated by endothelin-1 and other vasoconstrictors in the human internal mammary artery (IMA).

Methods: Isolated IMA rings (n = 192, taken from 49 patients) were studied in organ bath for the interaction between endothelin-1, angiotensin II, U46619, and potassium chloride and the antagonist for ET_A (BQ-123) or ET_B (BQ-788).

Results: Significant relaxations were observed by BQ-123 (agonist: endothelin-1, 84.9 ± 7.9%; angiotensin II, 45.5 ± 5.1%; and U46619, 30.7 ± 5.7%) or BQ-788 (agonist: endothelin-1, 66.5 ± 11.3%; angiotensin II, 38.9 ± 4.2%; and U46619, 30.8 ± 4.0%), but not to potassium chloride-induced precontraction. Incubation of IMA with BQ-123 or BQ-123 + BQ-788 significantly shifted the concentration-contraction curve to endothelin-1 rightward (p < 0.05 vs control) with effective concentration causing 50% of maximal response (EC₅₀) (–7.59 ± 0.04 or –7.81 ± 0.05 vs –8.47 ± 0.05 log M in the control, p < 0.001), whereas BQ-788 alone did not affect the contraction curve (p = 1.0 vs control). In contrast, none of the endothelin-1 inhibitors and the combination demonstrated significant depression effects on angiotensin II, U46619, or potassium chloride-induced contraction.

Conclusions: The present study demonstrates the role of ET_A and ET_B antagonists in the endothelin-1-mediated contraction in the human IMA and indicates the dominant role of ET_A receptors. Although these effects are specific to endothelin-1, cross-action between endothelin-1 and angiotensin II exists. These findings provide useful knowledge for the future development of the clinical antispastic protocol in coronary bypass surgery.