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

The hypothesized that the cytoskeletal network in vascular smooth muscle ce lls (VSMC) is critical to the signaling pathways from angiotensin (ANG) II- receptor subtype 1 (AT(1)) activation to intracellular Ca2+ (Ca-i(2+)) rele ase from internal stores and Ca2+ influx. This was tested in spontaneously hypertensive rats (SHR), in which differences were reported in cultured aor tic VSMC Ca-i(2+) regulation and G protein function compared with those in normotensive Wistar-Kyoto (WKY) rats. In cultured aortic VSMC, disorganizat ion of actin filaments with cytochalasin D (2 mu mol/l) decreased the ANG I I-induced Ca-i(2+) release from internal stores and the ANG II-induced Ca2 influx in SHR in a reversible fashion, whereas it was without effect in WK Y rats. On the other hand, blocking the dynamic state of the microtubule ne twork significantly reduced ANG II-induced Ca-i(2+) release from internal s tores 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 pl ay a major role in linking AT(1)-receptor activation to both Ca-i(2+) relea se mechanisms and capacitative Ca2+ influx. Furthermore, a functionally int act microtubule system is a necessary prerequisite for ANG II-induced Ca-i( 2+) release in both strains.