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(Hypertension. 2000;35:280.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Endothelin-Mediated Calcium Signaling in Preglomerular Smooth Muscle Cells

Alan C. Schroeder; John D. Imig; Elizabeth A. LeBlanc; Bao Thang Pham; David M. Pollock; Edward W. Inscho

From Louisiana State University, School of Medicine, New Orleans (A.C.S.); the Vascular Biology Center, Medical College of Georgia, Augusta (D.M.P.); and the Department of Physiology, Tulane University School of Medicine, New Orleans, La (J.D.I., E.A.L., B.T.P., E.W.I.).

Correspondence to Edward W. Inscho, PhD, Department of Physiology SL#39, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112. E-mail einscho{at}mailhost.tcs.tulane.edu

Abstract—This study was performed to test the hypothesis that endothelin peptides differentially influence intracellular calcium concentration ([Ca²⁺]_i) in preglomerular microvascular smooth muscle cells (MVSMC), in part through activation of endothelin (ET)_A receptors. Experiments were performed in vitro with the use of single MVSMC freshly isolated from rat preglomerular microvessels. 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 microscopy 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 nmol/L, respectively. The time course of the [Ca²⁺]_i response was biphasic, beginning with a rapid initial increase followed by a sustained plateau phase or a period during which [Ca²⁺]_i oscillated sharply. Similar responses were observed after ET-2 administration. In contrast, ET-3 stimulated monophasic increases in [Ca²⁺]_i of only 14±5, 33±16, and 44±19 nmol/L at peptide concentrations of 1, 10, and 100 nmol/L, respectively. These responses are significantly smaller than responses to ET-1 or ET-2, respectively. The relative contributions of calcium mobilization and calcium influx in the response to ET-1 were also evaluated. Removal of calcium from the 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 demonstrate that endothelin peptides increase [Ca²⁺]_i in preglomerular MVSMC. The concentration-response profiles are consistent with the response involving activation of ET_A receptors. Furthermore, these results suggest that ET-1 increases [Ca²⁺]_i by stimulating both the release of intracellular calcium and the influx of calcium from the extracellular medium.

Key Words: endothelin • calcium • microcirculation • receptors, endothelin

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