Angiotensin II and Intracellular Calcium of Adult Cardiac Fibroblasts

Abstract In various cardiovascular disorders, circulating or myocardial angiotensin II (Ang II) levels are increased, leading to excess collagen synthesis of cardiac fibroblasts. To characterize signal transduction mechanisms of Ang II, we examined changes in intracellular Ca 2+ concentration ([Ca 2+ ] i ) of fura-2-loaded cultured adult rat cardiac fibroblasts by fluorescence photometry. [Ca 2+ ] i was increased by Ang II via AT 1 receptors in a dose-dependent manner (EC 50 =2.4×10 −8 mol/l) involving two distinct phases, an initial Ca 2+ peak and a sustained elevated plateau phase. The initial Ca 2+ peak occurred transiently and independently of the duration of Ang II application. While the magnitude of the transient Ca 2+ peak did not differ in a nominally Ca 2+ -free (3 mmol/l EGTA) solution, the Ang II-mediated sustained plateau phase of [Ca 2+ ] i was dependent on extracellular Ca 2+ . Thus, the initial transient Ca 2+ peak appears to arise from intracellular Ca 2+ stores, whereas the plateau phase involves an external Ca 2+ influx. Since collagen synthesis of cardiac fibroblasts is maximally stimulated by Ang II or by fetal bovine serum (FBS), the effects of Ang II and FBS on [Ca 2+ ] i were compared. The magnitude of the transient Ca 2+ peak induced by 10 −7 mol/l Ang II was comparable to that of 10% FBS indicating that the rise in [Ca 2+ ] i might be involved in the signal transduction pathway of Ang II-mediated collagen synthesis of cardiac fibroblasts.