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

OBJECTIVES We 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. DESIGN The 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). METHODS Intact 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 micromol/l) was measured by enzyme immunoassay. RESULTS In isolated aortas from TG rats, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 micromol/l) or the CysLT1 receptor antagonist (MK571, 1 micromol/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 AT1 receptor antagonist losartan (1 micromol/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. CONCLUSION These data suggest that CysLTs are involved in the contractile responses to Ang II in isolated aortas from TG but not from SD rats.