ANG II-induced Ca(2+) increase in smooth muscle cells from SHR is regulated by actin and microtubule networks.
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.
Samain
E
E
Institut National de la Santé et de la Recherche Médicale U337, Faculté Broussais-Hotel Dieu, 75006 Paris, France.
Bouillier
H
H
Perret
C
C
Safar
M
M
Dagher
G
G
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
D000199:Actins; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D019284:Thapsigargin; D002118:Calcium