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Involvement of cysteinyl leukotrienes in angiotensin II-induced contraction in isolated aortas from transgenic (mRen-2)27 rats

 

作者: Françoise Stanke-Labesque,   Gaëlle Hardy,   Sabrina Vergnaud,   Philippe Devillier,   Michel Peoc'h,   Jacques Randon,   Giampierro Bricca,   Françoise Caron,   Jean Cracowski,   Germain Bessard,  

 

期刊: Journal of Hypertension  (OVID Available online 2002)
卷期: Volume 20, issue 2  

页码: 263-272

 

ISSN:0263-6352

 

年代: 2002

 

出版商: OVID

 

关键词: angiotensin II;5-lipoxygenase;leukotriene receptor;rat thoracic aorta;hypertension

 

数据来源: OVID

 

摘要:

ObjectivesWe have previously reported that 5-lipoxygenase-derived products, and particularly the cysteinyl leukotrienes (CysLTs), were involved in angiotensin II (Ang II)-induced contractions in isolated aortas from spontaneously hypertensive rats.DesignThe aim of this study was to assess the role of CysLTs in the vascular response to Ang II in an Ang II-dependent model of hypertension, the (mRen-2)27 transgenic rats (TGs).MethodsIntact aortic rings from TG and normotensive Sprague–Dawley rats (SDs) were suspended in organ chambers for isometric tension development in response to Ang II. In addition, the release of CysLTs in response to Ang II (0.3 μmol/l) was measured by enzyme immunoassay.ResultsIn isolated aortas from TG rats, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 μmol/l) or the CysLT1receptor antagonist (MK571, 1 μmol/l) significantly (P<0.05) reduced Ang II-induced contractions by 52 and 42%, respectively. In addition, Ang II induced a 2.6-fold increase in CysLT release (pg/mg dry weight tissue: 58.3±17.9 (Ang II,n= 7) versus 22.5±5.9 (basal,n= 7)P<0.05), which was inhibited by the AT1receptor antagonist losartan (1 μmol/l). In contrast, in aortas from SD rats, pretreatment with AA861 or MK571 did not alter Ang II-induced contraction and CysLT production remained unchanged after exposure to Ang II.ConclusionThese data suggest that CysLTs are involved in the contractile responses to Ang II in isolated aortas from TG but not from SD rats.

 

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