BASAL AND ANGIOTENSIN-II-INDUCED CYTOSOLIC-FREE CALCIUM IN ADULT-RAT CARDIOMYOCYTES AND FIBROBLASTS AFTER VOLUME OVERLOAD

This study investigates basal and angiotensin II (Ang II)-induced [Ca2 +](i) concentrations in cells from hearts of rats that have undergone cardiac hypertrophy due to volume overload. [Ca2+](i) measurements ass essed by digital imaging using fura 2 methodology were performed on is olated ventricular cardiomyocytes and fibroblasts from adult rat heart s with a 4-week aortocaval shunt. Long-term aortocaval shunt induced a significant increase in atrial (72%) and ventricular (41%) weights an d a large elevation in plasma atrial natriuretic peptide-(1-98) concen tration (160%). For adult cardiomyocytes [Ca2+](i) measurements are re ported as diastolic (average of the lowest points) and systolic intrac ellular Ca2+ values (average of the maximum points corresponding to th e diastolic points) over a 30-second time interval. Basal diastolic [C a2+](i) (99+/-4.1 nmol/L for experimental cells versus 90+/-4.8 for co ntrol cells) was not altered, whereas basal systolic [Ca2+](i) was sig nificantly greater in ventricular cardiomyocytes from overload hearts (155+/-2.3 versus 129+/-4.4 nmol/L for control cells, P<.05). Ang II i ncreased intracellular Ca2+ spike frequency in a concentration-depende nt manner in cardiomyocytes from control and overload myocardium. Basa l and Ang II-induced intracellular Ca2+ spike frequencies were not mod ified in cardiomyocytes from hypertrophied hearts. Basal [Ca2+](i) in ventricular fibroblasts from overload myocardium was significantly inc reased (128+/-5.1 nmol/L for fibroblasts from hyper trophied hearts ve rsus 104+/-3.5 for control cells, P<.05). Ang II-induced [Ca2+](i) was lower in fibroblasts from overload myocardium (P<.05). In conclusion, alterations of intracellular calcium homeostasis in the two predomina nt cardiac cell types involved in myocardial growth and fibrosis, card iomyocytes and fibroblasts, respectively, may contribute to the physio pathology of heart failure in adult rats. Ang II signaling through the intracellular calcium transduction pathway in a cell-specific manner may play an important role in cardiac hypertrophy.