AJP - Heart and Circulatory Physiology, Vol 268, Issue 5 2009-H2016, Copyright © 1995 by American Physiological Society
Potentiation of angiotensin II-stimulated vascular contraction by lithium
M. E. Ullian, L. G. Walsh, K. C. Wong and C. J. Allan
Department of Medicine, Medical University of South Carolina, Charleston 29425, USA.
Previous studies have suggested that lithium prolongs or enhances vascular
contractions stimulated by alpha-adrenergic agents. The present study was
performed to determine whether a similar phenomenon occurs with angiotensin
II (ANG II)-stimulated contractions and whether this phenomenon results
from interactions with the phosphoinositide signaling system. Contractions
of rat aortic rings with 100 nM ANG II were 38% greater in the presence of
20 mM LiCl than in its absence (0.47 +/- 0.07 vs. 0.34 +/- 0.05 g
tension/mg dry tissue wt, P < 0.01). The effects of lithium on inositol
phosphate responses, diacylglycerol responses, and intracellular calcium
concentration on single or repeated stimulations with ANG II were then
examined in vascular smooth muscle cells cultured from rat aorta. Cells
exposed twice to 100 nM ANG II contained 50% lower inositol trisphosphate
levels (InsP3) and 10% lower diacylglycerol levels than cells exposed to
ANG II only once. LiCl or lithium acetate abolished these desensitizations
in a concentration-dependent manner. Similarly, InsP3 and diacylglycerol
responses to a single exposure of ANG II were heightened by lithium (by 75
and 25%, respectively), and the duration of the responses was prolonged by
lithium (5- and 2-fold, respectively). In contrast, ANG II-stimulated
calcium transients were not enhanced or prolonged by lithium, nor was
desensitization of ANG II-stimulated cytosolic calcium mobilization upon
serial exposures abolished by lithium. When ring contraction studies were
repeated in the presence of the protein kinase C inhibitor staurosporine
(150 nM), lithium no longer potentiated ANG II contractions [0.38 +/- 0.03
(control) vs. 0.35 +/- 0.06 g tension/mg dry tissue wt (lithium)].(ABSTRACT
TRUNCATED AT 250 WORDS)
