Angiotensin ii-induced ca2+-oscillations in vascular myocytes from
the rat pulmonary artery.
Guibert, Christelle, Roger Marthan, and Jean-Pierre Savineau.
Laboratoire de Physiologie, Universit[acute]e Bordeaux 2, 146 rue
L[acute]eo Saignat, 33076 Bordeaux Cedex
APStracts 2:0215L, 1995.
The effect of angiotensin II (AII) on the cytosolic calcium
concentration ([Ca2+]i) was studied in freshly (2-8 hours) 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 AII (0.01 to 10 [mu]M) induced cyclic variations
(oscillations) in [Ca2+]i. The AII-induced response was typically
composed of 3 to 6 oscillations of constant duration (9.8 +/- 0.5 s,
n = 40) but of decreasing amplitude. The first oscillation increased
[Ca2+]i from 119 +/- 4 to 884 +/- 33 nM (n = 32). AII-induced
response was concentration-dependently inhibited by previous addition
to the bathing solution of losartan or SR47436 (0.01-0.1 [mu]M,
each), two specific AT1 receptor-antagonists. In Ca2+-free external
solutions (containing 0.4 to 1 mM EGTA), AII still produced
oscillation in [Ca2+]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 AII,
caffeine (0.5-10 mM) induced only one transient rise in [Ca2+]i which
was unaltered by neomycin or PDBu but blocked by thapsigargin. These
results show that AII produces oscillations in [Ca2+]i in pulmonary
arterial myocytes via stimulation of AT1 receptors coupled to
phospholipase C activation. AII-induced oscillations appear to be
related to the cycling of Ca2+ ions from an intracellular store
(presumably the sarcoplasmic reticulum) by a primarily inositol
trisphosphate-dependent Ca2+ release.
Received 5 July 1995; accepted in final form 15 November 1995.
APS Manuscript Number L211-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95