title: ANG II-induced Ca(2+) 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 (AT(1)) activation to intracellular Ca(2+) (Ca(2+)(i)) release from internal stores and Ca(2+) influx. This was tested in spontaneously hypertensive rats (SHR), in which differences were reported in cultured aortic VSMC Ca(2+)(i) 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 micromol/l) decreased the ANG II-induced Ca(2+)(i) release from internal stores and the ANG II-induced Ca(2+) 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 Ca(2+)(i) release from internal stores but was without effect on Ca(2+) 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 AT(1)-receptor activation to both Ca(2+)(i) release mechanisms and capacitative Ca(2+) influx. Furthermore, a functionally intact microtubule system is a necessary prerequisite for ANG II-induced Ca(2+)(i) release in both strains.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U337, Faculté Broussais-Hotel Dieu, 75006 Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Samain
authors.forename: H
authors.initials: H
authors.lastname: Bouillier
authors.forename: C
authors.initials: C
authors.lastname: Perret
authors.forename: M
authors.initials: M
authors.lastname: Safar
authors.forename: G
authors.initials: G
authors.lastname: Dagher
mesh_terms: D000199:Actins / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D019284:Thapsigargin; D002118:Calcium