Cysteinyl leukotriene-dependent [Ca ]i responses to angiotensin II in cardiomyocytes

Liu, Pinggang, Derek A. Misurski, and Venkat Gopalakrishnan. Cysteinyl leukotriene-dependent [Ca2 ]i responses to angiotensin II in cardiomyocytes. Am J Physiol Heart Circ Physiol 284: H1269–H1276, 2003. First published December 12, 2002; 10.1152/ajpheart.00303.2002.—With the use of fura 2 measurements in multiple and single cells, we examined whether cysteinyl leukotrienes (CysLT) mediate angiotensin II (ANG II)-evoked increases in cytosolic free Ca2 concentration ([Ca2 ]i) in neonatal rat cardiomyocytes. ANG II-evoked CysLT release peaked at 1 min. The angiotensin type 1 (AT1) antagonist losartan, but not the AT2 antagonist PD-123319, attenuated the elevations in [Ca2 ]i and CysLT levels evoked by ANG II. Vasopressin and endothelin-1 increased [Ca2 ]i but not CysLT levels. The 5-lipoxygenase (5-LO) inhibitor AA-861 and the CysLT1-selective antagonist MK-571 reduced the maximal [Ca2 ]i responses to ANG II but not to vasopressin and endothelin-1. While MK-571 reduced the responses to leukotriene D4 (LTD4), the dual CysLT antagonist BAY-u9773 completely blocked the [Ca2 ]i elevation to both LTD4 and LTC4. These data confirm that ANG II-evoked increases, but not vasopressinand endothelin-1-evoked increases, in [Ca2 ]i involve generation of the 5-lipoxygenase metabolite CysLT. The inositol (1,4,5)trisphosphate [Ins(1,4,5)P3] antagonist 2-aminoethoxydiphenyl borate attenuated the [Ca2 ]i responses to ANG II and LTD4. Thus AT1 receptor activation by ANG II is linked to CysLT-mediated Ca2 release from Ins(1,4,5)P3-sensitive intracellular stores to augment direct ANG II-evoked Ca2 mobilization in rat cardiomyocytes.