- Using fura-2 measurement in multiple and single cells, we examined whether cysteinyl leukotrienes (CysLT) mediate angiotensin II (ANG II) evoked increases in [Ca²⁺]_i in neonatal rat cardiomyocytes. ANG II evoked CysLT release peaked at 1 min. The AT₁ antagonist, losartan, but not the AT₂ antagonist, PD123319, 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, AA861, and the CysLT₁ selective antagonist, MK571, reduced the maximal [Ca²⁺]_i responses to ANG II but not to vasopressin and endothelin-1. While MK571 reduced the responses to leukotriene D₄, the dual CysLT antagonist, BAYu9773, completely blocked the [Ca²⁺]_i elevation to both LTD ₄ and leukotriene C ₄. These data confirm that ANG II but not vasopressin and endothelin-1 evoked increases in [Ca²⁺]_i involves generation of 5-LO metabolites, CysLT. The InsP₃ antagonist, 2-aminoethoxydiphenyl borate, attenuated the [Ca²⁺]_i responses to ANG II, LTD₄. Thus, AT₁ receptor activation by ANG II is linked to CysLT mediated Ca²⁺ release from InsP₃ sensitive intracellular stores to augment direct ANG II evoked Ca²⁺ mobilization in rat cardiomyocytes.