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Mediators of Inflammation
Volume 4, Issue 6, Pages 417-425
http://dx.doi.org/10.1155/S0962935195000676

Role of lipoxygenase products in the effects of angiotensin II in the isolated aorta and perfused heart of the rat

1Utrecht University, Faculty of Pharmacy, Department of Pharmacoepidemiology & Pharmacotherapy, P.O. Box 80 082, Utrecht 3508 TB, The Netherlands
2National Institute of Public Health and Environmental Protection, P.O. Box 1, Bilthoven 3720 BA, The Netherlands
3University Hospital Utrecht, Department of Cardiology, Heart Lung Institute, P.O. Box 85 500, Utrecht 3508 GA, The Netherlands
4pharma Bio-Research, Science Park, P.O. Box 200, Zuidlaren 9470 AE, The Netherlands
5University Hospital Utrecht, Department of Cardiology, Heart Lung Institute, G02.523, P.O. Box 85 500, Utrecht 3508 GA, The Netherlands

Copyright © 1995 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The objective of this study was to determine whether arachidonate metabolites are involved in the vasoconstrictive effects of angiotensin II in rats. In the isolated perfused heart, dexamethasone (4 mg/kg) significantly suppressed the maximal decreases in coronary flow induced by angiotensin II and vasopressin (reference drug). In the heart, the nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1 μM) markedly suppressed the angiotensin II-induced decreases in coronary flow. NDGA (10 μM) inhibited both angiotensin II- and methoxamine- (reference drug) induced contractions in aortic rings with (in the presence of L-NAME) and without endothelium. In the heart, the leukotriene synthesis inhibitor MK-886 (0.3 μM) significantly reduced the maximal effects to angiotensin II, but the leukotriene antagonist FPL 55712 (0.1 and 0.3 μM) had no effect. We conclude that in the isolated perfused rat heart angiotensin II-induced decreases in coronary flow are in part mediated by Hpoxygenase products, which might be derived from the 5-Hpoxygenase pathway, but are probably not leukotrienes. Furthermore, endothelium independent Hpoxygenase products mediate part of the contractile responses to angiotensin II in the isolated rat aorta.