Endothelin-mediated calcium signaling in preglomerular smooth muscle cells

Citation
Ac. Schroeder et al., Endothelin-mediated calcium signaling in preglomerular smooth muscle cells, HYPERTENSIO, 35(1), 2000, pp. 280-286
Citations number
34
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
HYPERTENSION
ISSN journal
0194911X → ACNP
Volume
35
Issue
1
Year of publication
2000
Part
2
Supplement
S
Pages
280 - 286
Database
ISI
SICI code
0194-911X(200001)35:1<280:ECSIPS>2.0.ZU;2-N
Abstract
This study was performed to test the hypothesis that endothelin peptides di fferentially influence intracellular calcium concentration ([Ca2+](i)) in p reglomerular microvascular smooth muscle cells (MVSMC), in part through act ivation of endothelin (ET)(A) receptors. Experiments were performed in vitr o with the use of single MVSMC freshly isolated from rat preglomerular micr ovessels. The effect of ET-1, ET-2, and ET-3 on [Ca2+](i) was measured with the use of the calcium-sensitive dye, fura 2, and standard fluorescence mi croscopy techniques. Baseline [Ca2+](i) averaged 84+/-3 nmol/L (n=141 cells from 23 dispersions). ET-1 concentrations of 1, 10, and 100 nmol/L, evoked peak increases in [Ca2+](i) of 48 +/- 16, 930 +/- 125, and 810 +/- 130 nmo l/L, respectively. The time course of the [Ca2+](i) response was biphasic, beginning with a rapid initial increase followed by a sustained plateau pha se or a period during which. [Ca2+](i) oscillated sharply. Similar response s were observed after ET-2 administration, In contrast, ET-3 stimulated mon ophasic increases in [Ca2+](i) of only 14 +/- 5, 33 +/- 16, and 44 +/- 19 n mol/L at peptide concentrations of 1, 10, and 100 nmol/L, respectively. The se responses are significantly smaller than responses to ET-1 or ET-2, resp ectively. The relative contributions of calcium mobilization and calcium in flux in the response to ET-1 were also evaluated. Removal of calcium from t he bathing medium did not significantly alter the peak response to 10 nmol/ L ET-1 but abolished the late phase elevation of [Ca2+](i). These data demo nstrate that endothelin peptides increase [Ca2+](i) in preglomerular MVSMC. The concentration-response profiles are consistent with the response invol ving activation of ETA receptors. Furthermore, these results suggest that E T-1 increases [Ca2+](i) by stimulating both the release of intracellular ca lcium and the influx of calcium from the extracellular medium.