Angiotensin II and intracellular calcium of adult cardiac fibroblasts.
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 Ca2+ concentration ([Ca2+]i) of fura-2-loaded cultured adult rat cardiac fibroblasts by fluorescence photometry. [Ca2+]i was increased by Ang II via AT1 receptors in a dose-dependent manner (EC50 = 2.4 x 10(-8) mol/l) involving two distinct phases, an initial Ca2+ peak and a sustained elevated plateau phase. The initial Ca2+ peak occurred transiently and independently of the duration of Ang II application. While the magnitude of the transient Ca2+ peak did not differ in a nominally Ca(2+)-free (3 mmol/l EGTA) solution, the Ang II-mediated sustained plateau phase of [Ca2+]i was dependent on extracellular Ca2+. Thus, the initial transient Ca2+ peak appears to arise from intracellular Ca2+ stores, whereas 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 10(-7) mol/l Ang II was comparable to that of 10% FBS indicating that the rise in [Ca2+]i might be involved in the signal transduction pathway of Ang II-mediated collagen synthesis of cardiac fibroblasts.
Brilla
C G
CG
Molecular Cardiology Laboratory, Philipps University of Marburg, Germany.
Scheer
C
C
Rupp
H
H
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005312:Fetal Blood; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D016257:Fura-2; D006352:Heart Ventricles / Q000166:cytology* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013050:Spectrometry, Fluorescence / Q000379:methods; D013777:Tetrazoles / Q000494:pharmacology
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D003470:Culture Media; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D004533:Egtazic Acid; D003094:Collagen; C081643:candesartan; D002118:Calcium; D016257:Fura-2