Abstract
Angiotensin (ANG) II is present inside vascular smooth muscle cells (VSMC); however, its intracellular functions if any, are unknown. We tested the hypothesis that intracellular ANG II exerts effects on cytosolic calcium [Ca++]i in VSMC. ANG II was administered via microinjection. Microinjection of ANG II led to a rapid increase in [Ca++]i in the cytosol and in the nucleus. The [Ca++]i increase was due to the influx of extracellular Ca++ ions. The intracellular ANG II effect was totally inhibited by the concomitant injection of the ANG II antagonist CV-11947. Desensitization of extracellular ANG II receptors on the other hand, did not influence the intracellular effects, nor did extracellular CV-11947. The increase in [Ca++]i was not only observed in the microinjected cell, but also in directly adjacent VSMC. In contrast to the microinjected cells, the [Ca++]i increase in the adjacent cells was mostly due to release from intracellular stores. Pretreatment with thapsigargin abolished the ANG II response in adjacent cells. Microinjection of IP3 induced a [Ca++]i response in adjacent cells which was similar to the ANG II-induced effects. Preincubation of VSMC with the uncoupling substances DMSO and heptanol did not decrease the ANG II response, but instead prevented a [Ca++]i surge in adjacent cells. We conclude that intracellular ANG II binds to intracellular ANG II receptors and elicits an increased [Ca++]i in the injected cell and thereafter cells in the immediate neighborhood. Cell-cell contact is necessary for the ANG II-mediated effects. The data suggest that ANG II-related effects may be amplified by an intracellular action.
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Haller, H., Luft, F. Angiotensin II acts intracellularly in vascular smooth muscle cells. Basic Res Cardiol 93 (Suppl 2), s030–s036 (1998). https://doi.org/10.1007/s003950050204
Issue Date:
DOI: https://doi.org/10.1007/s003950050204