© 1997 American Heart Association, Inc.
Articles |
Cross Talk Between Angiotensin AT1 and 
1-Adrenergic Receptors
Angiotensin II Downregulates 1a-Adrenergic Receptor Subtype mRNA and Density in Neonatal Rat Cardiac Myocytes
From the Cardiology Section, Veterans Affairs Medical Center, the Cardiovascular Research Institute, and the Department of Medicine, University of California, San Francisco.
Correspondence to Joel S. Karliner, MD, Cardiology Section (111C), Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA 94121. E-mail Karliner.Joel-S{at}SanFrancisco.VA.Gov
Abstract Signaling mediated by the angiotensin
(Ang) II and 1-adrenergic receptor (1-AR)
pathways is important for cardiovascular homeostasis.
However, it is unknown whether Ang II has any direct effect on
1-AR expression and signaling in cardiac myocytes. In
the present study, we determined 1-AR subtype mRNA
levels by RNase protection; receptor density by competition binding
with 5-methylurapidil; and 1-AR mediated
c-fos expression by Northern blot analysis. We found
that Ang II had no effect on 1b- and
1d-AR mRNA levels but decreased the 1a-AR
mRNA level in a time- and dose-dependent manner. The maximal effect
occurred at 6 hours with 100 nmol/L Ang II (40.0±8.2% reduction, n=4,
P<.01). The decrease in 1a-AR mRNA level
induced by Ang II is mediated by the Ang II AT1
receptor subtype and is associated with decreased stability of
1a-AR mRNA. Corresponding to the changes in the
1a-AR mRNA level, Ang II (100 nmol/L, 24 hours) reduced
the density of high-affinity sites for 5-methylurapidil
(1A-AR) by 29% (56.5±6.4 versus 79.0±11.6 fmol/mg
protein, n=4, P<.05). 1-AR stimulated
c-fos induction, which could be blocked by 5-methylurapidil
but not by chloroethylclonidine, was attenuated by Ang II preincubation
(100 nmol/L, 24 hours). We conclude that there is previously
undescribed cross talk between AT1 receptors and
1-ARs. Ang II selectively downregulates
1a-AR subtype mRNA and its corresponding receptor as
well as 1a-AR mediated expression of the
immediate-early gene c-fos in cardiac myocytes.
Key Words: 1-adrenergic receptor • angiotensin II • cardiac myocyte • immediate-early gene
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