Angiotensin II-induced Ca (2+) -oscillations in vascular myocytes from the rat pulmonary artery
Guibert, C.; Marthan, R.; Savineau, J.P.
American Journal of Physiology 270(4 Pt 1): L637-L642
1996
ISSN/ISBN: 0002-9513 PMID: 8928824 Document Number: 456092
The effect of angiotensin II (ANG II) on the cytosolic calcium concentration ((Ca-2+)-i) was studied in freshly (2-8 h) isolated myocytes from the main pulmonary artery of the rat. Myocytes were loaded with the fluorescent indicator indo 1 (1 mu-M for 30 min) and experiments were performed at room temperature. Short (30 s) applications of ANG II (0.01-10 mu-M) induced cyclic variations (oscillations) in (Ca-2+)-i. The ANG II-induced response was typically composed of three to six oscillations of constant duration (9.8 +- 0.5 s, n = 40) but of decreasing amplitude. The first oscillation increased (Ca-2+)-i from 119 +- 4 to 884 +- 33 nM (n = 32). ANG II-induced response was concentration dependently inhibited by previous addition to the bathing solution of losartan or SR-47436 (0.01-0.1 mu-M, each), two specific AT-1 receptor-antagonists. In Ca-2+-free external solutions (containing 0.4-1 mM EGTA), ANG II still produced oscillation in (Ca-2+)-i. These oscillations disappeared in myocytes pretreated with neomycin (0.1 mu-M), thapsigargin (1 mu-M), or phorbol 12,13-dibutyrate (PDBu, 1 mu-M). In contrast to ANG II, caffeine (0.5-10 mM) induced only one transient rise in (Ca-2+)-i, which was unaltered by neomycin or PDBu but blocked by thapsigargin. These results show that ANG II produces oscillations in (Ca-2+)-i in pulmonary arterial myocytes via stimulation of AT-1 receptors coupled to phospholipase C activation. ANG II-induced oscillations appear to be related to the cycling of Ca-2+ ions from an intracellular store (presumably the sarcoplasmic reticulum) by a primarily inositol trisphosphate-dependent Ca-2+ release.