© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Angiotensin II-induced contractions in human internal mammary artery: effects of cyclooxygenase and lipoxygenase inhibition
aLaboratory of Pharmacology, University of Medicine, LSCPA EA2937, F-38706 La Tronche, Cedex, France
bLaboratory of Pharmacology, Maison Blanche Hospital, F-51092 Reims, France
cDepartment of Cardiac Surgery, Albert Michallon Hospital, CHU Grenoble, BP217, F-38043 Grenoble, Cedex 9, France
* Corresponding author. Tel.: +33-4-7663-7159; fax: +33-4-7651-8667 francoise.stanke{at}ujf-grenoble.fr
Objective: This study investigated, in isolated human internal mammary artery, the involvement of the cyclooxygenase and the lipoxygenase pathways of arachidonic acid metabolism in the contraction induced by angiotensin II. Methods: Rings of human internal mammary arteries were suspended in organ baths for recording of isometric tension. In addition, the release of eicosanoids in response to angiotensin II (0.3 µM) was measured by enzyme immunoassay. Results: In human arterial rings without endothelial dependent relaxation in response to substance P or acetylcholine, the angiotensin II-induced contractions were significantly (P<0.05) reduced by 27% in the presence of GR32191 0.3 µM (thromboxane A2 (TXA2) receptor antagonist) but remained unchanged in the presence of dazoxiben 100 µM (thromboxane synthase inhibitor). In addition, angiotensin II failed to modify TXB2 and 6-keto-PGF1
production. These results suggest the contribution of a TXA2/PGH2 agonist other than TXA2 in angiotensin II-induced contractions. However, indomethacin increased (P<0.05) angiotensin II-mediated contractile response and cysteinyl leukotriene production, suggesting a redirection of arachidonic acid metabolism from the cyclooxygenase pathway to the lipoxygenase pathway. Indeed, the contractions induced by angiotensin II were inhibited (P<0.05) by phenidone 100 µM (cyclooxygenase and lipoxygenase inhibitor), baicalein 100 µM (5-, 12- and 15-lipoxygenases inhibitor), AA861 10 µM (5-lipoxygenase inhibitor) and MK571 1 µM (CysLT1 receptor antagonist). Cysteinyl leukotrienes were released in response to angiotensin II (pg/mg dry weight tissue: 32±9 (basal, n=6) vs. 49±9 (angiotensin II 0.3 µM, n=6), P<0.05). LTD4, and at a lesser degree LTC4, induced contractions of internal mammary artery and MK571 1 µM abolished the contraction to LTD4. Conclusions: This study suggests that the in vitro vasoconstrictor effects of angiotensin II in human internal mammary artery are enhanced at least in part by eicosanoids produced by the cyclooxygenase pathway, probably PGH2, acting on TXA2/PGH2 receptors, and by lipoxygenase-derived products, particularly cysteinyl leukotrienes acting on CysLT1 receptors.
KEYWORDS Angiotensin; Arteries; Lipid metabolism; Prostaglandins; Receptors
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Tong Chuang Feng, Wang Yui Ying, Ren Jang Hua, Y. Y Ji, and M. de Gasparo Effect of valsartan and captopril in rabbit carotid injury. Possible involvement of bradykinin in the antiproliferative action of the renin-angiotensin blockade Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1): 19 - 24. [Abstract] [PDF]
|
|