(Hypertension. 2001;37:1423.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Expression and Distribution of NOS1 and NOS3 in the Myocardium of Angiotensin II–Infused Rats
From the Department of Internal Medicine, School of Medicine, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Correspondence to Kleber G. Franchini, MD, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Cidade Universitária "Zefferino Vaz," 13081-970 Campinas, SP, Brasil. E-mail franchin{at}obelix.unicamp.br
Abstract—Studies
have indicated a complex functional interaction between
angiotensin (Ang) II and NO in the heart. The purpose of
the present study was to examine the protein expression and tissue
distribution of NO synthases 1 (NOS1) and 3 (NOS3) in the
myocardium of rats that underwent continuous infusion of
Ang II at 2 different rates (10 and 40 ng ·
kg-1 ·
min-1) for 6 days. Mean
arterial pressure increased by 
15 mm Hg in rats
infused with Ang II at 40 ng · kg-1 ·
min-1, but it remained close to the values
observed in saline-infused rats (110 mm Hg) when Ang II was
infused at 10 ng · kg-1 ·
min-1. The protein expression of a 160-kDa
NOS1 and a 135-kDa NOS3 were found to increase (200%) in the
myocardium of rats infused with both subpressor and pressor
doses of Ang II. Immunohistochemistry studies showed that NOS1 and NOS3
are differentially expressed in myocardial cells. NOS1 was detected in
cardiac myocytes and in smooth muscle cells of small and large
coronary arteries, whereas NOS3 was detected in the
endothelium and in perivascular and
interstitial tissues, but NOS3 was not detected in cardiac
or smooth muscle cells. Ang II infusion enhanced the tissue
immunoreactivity of both isoforms in their specific locations but did
not change the distribution throughout the myocardium.
Myocardium staining with anti–angiotensin type
1 (AT1) receptor antibody indicated that
AT1 receptor is expressed in cardiac myocytes,
coronary smooth muscle cells, and interstitial and
perivascular tissues. Ang II infusion did not change the protein
expression and distribution of AT1 receptor in
the myocardium. These results indicate that long-term
increases in the circulating levels of Ang II modulate the protein
expression of NOS1 and NOS3 and, consequently, the function of the
local myocardial NO system.
Key Words: angiotensin II • nitric oxide • nitric oxide synthase • heart • myocardium
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