© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Cysteinyl leukotrienes are involved in angiotensin II-induced contraction of aorta from spontaneously hypertensive rats
Laboratory of Pharmacology, University of Medicine, LSCPA EA2937 F-38706, La Tronche Cedex, France
* Corresponding author. Tel.: +33-4-7663-7159; fax: +33-4-7651-8667 Francoise.Stanke{at}ujf-grenoble.fr
Objective: Non specific lipoxygenase inhibitors have been reported to reduce the in vitro constrictor response and the in vivo pressor effect of angiotensin II in rats. The aim of this study was to assess the role of cysteinyl leukotrienes, in the vascular response to angiotensin II in spontaneously hypertensive rats (SHR). Methods: Rings of thoracic aorta from SHR and normotensive Wistar–Kyoto rats (WKY) were compared in terms of contractile responses and release of cysteinyl leukotrienes in response to angiotensin II. Results: Pretreatment with the specific 5-lipoxygenase inhibitor AA861 10 µM reduced the efficacy of angiotensin II in intact and endothelium-denuded aorta from SHR (% inhibition vs. control: 65±12.6% with endothelium (n = 6), P<0.05; 43±7.2% without endothelium (n = 6), P<0.05) but not in aorta from WKY. In addition, in aorta from SHR, the CysLT1 receptor antagonist MK571 1 µM reduced by 55±6.1% (n = 6, P<0.05) the contractile effects of angiotensin II in rings with endothelium but not in endothelium-denuded rings. Angiotensin II induced a 8.6±2.1-fold increase in cysteinyl leukotriene production in aorta rings from SHR with endothelium which was prevented by the AT1 receptor antagonist losartan 1 µM but not by the AT2 receptor antagonist PD123319 0.1 µM. In aorta rings from WKY, cysteinyl leukotriene production remained unchanged after exposition to angiotensin II. The cysteinyl leukotrienes (up to 0.1 µM) induced contractions in aorta rings from SHR but not from WKY. Conclusions: These data suggest that cysteinyl leukotrienes, acting at least in part on endothelial CysLT1 receptors, are involved in the contractile response to angiotensin II in isolated aorta from SHR but not from WKY.
KEYWORDS Angiotensin; Arteries; Contractile function; Hypertension; Lipid metabolism; Receptors
1 Present address: Laboratory of Pharmacology, IFR 53, EA2070, Faculty of Medicine, F-51092 Reims, France.
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