ANG II-induced Ca2+ increase in smooth muscle cells from SHR is regulated by actin and microtubule networks

Abstract

We hypothesized that the cytoskeletal network in vascular smooth muscle cells (VSMC) is critical to the signaling pathways from angiotensin (ANG) II-receptor subtype 1 (AT1) activation to intracellular Ca2+([Formula: see text]) release from internal stores and Ca2+ influx. This was tested in spontaneously hypertensive rats (SHR), in which differences were reported in cultured aortic VSMC [Formula: see text]regulation and G protein function compared with those in normotensive Wistar-Kyoto (WKY) rats. In cultured aortic VSMC, disorganization of actin filaments with cytochalasin D (2 μmol/l) decreased the ANG II-induced [Formula: see text] release from internal stores and the ANG II-induced Ca2+influx in SHR in a reversible fashion, whereas it was without effect in WKY rats. On the other hand, blocking the dynamic state of the microtubule network significantly reduced ANG II-induced[Formula: see text] release from internal stores but was without effect on Ca2+ influx in either SHR or WKY rats. This study demonstrates for the first time that, in the SHR, actin filaments play a major role in linking AT1-receptor activation to both[Formula: see text] release mechanisms and capacitative Ca2+ influx. Furthermore, a functionally intact microtubule system is a necessary prerequisite for ANG II-induced [Formula: see text] release in both strains.