ANGIOTENSIN-II AND INTRACELLULAR CALCIUM OF ADULT CARDIAC FIBROBLASTS

In various cardiovascular disorders, circulating or myocardial angiote nsin II (Ang II) levels are increased, leading to excess collagen synt hesis of cardiac fibroblasts. To characterize signal transduction mech anisms of Aug II, we examined changes in intracellular Ca2+ concentrat ion ([Ca2+](i)) of fura-2-loaded cultured adult rat cardiac fibroblast s by fluorescence photometry. [Ca2+](i) was increased by Ang II via AT (1) receptors in a dose-dependent manner (EC50 = 2.4 x 10(-8) mol/l) i nvolving two distinct phases, an initial Ca2+ peak and a sustained ele vated plateau phase. The initial Ca2+ peak occurred transiently and in dependently of the duration of Ang II application. While the magnitude of the transient Ca2+ peak did not differ in a nominally Ca2+-free (3 mmol/l EGTA) solution, the Ang II-mediated sustained plateau phase of [Ca2+](i) was dependent on extracellular Ca2+. Thus, the initial tran sient Ca2+ peak appears to arise from intracellular Ca2+ stores, where as the plateau phase involves an external Ca2+ 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 [Ca2+](i ) were compared. The magnitude of the transient Ca2+ peak induced by 1 0(-7) mol/l Ang II was comparable to that of 10% FBS indicating that t he rise in [Ca2+], might be involved in the signal transduction pathwa y of Ang II-mediated collagen synthesis of cardiac fibroblasts. (C) 19 98 Academic Press.