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PMID: 7615784 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nitric oxide inhibits angiotensin II-induced migration of rat aortic smooth muscle cell. Role of cyclic-nucleotides and angiotensin1 receptors.

The Journal of clinical investigation ·Vol. 96 ·No. 1 ·1995-07-00 ·Pages 141-9

Dubey RK, Jackson EK, Lüscher TF

Abstract

Nitric oxide (NO) and angiotensin II (AII) can effect vascular smooth muscle cell (SMC) proliferation. However, the effects of such agents on SMC migration, an equally important phenomenon with regard to vascular pathophysiology, have received little attention. The objectives of the present study were: (a) to determine whether NO inhibits AII-induced migration of vascular SMCs; (b) to investigate the mechanism of the interaction of NO and AII on SMC migration; and (c) to evaluate the AII receptor subtype that mediates AII-induced SMC migration. Migration of rat SMCs was evaluated using a modified Boydens Chamber (transwell inserts with gelatin-coated polycarbonate membranes, 8 microns pore size). AII stimulated SMC migration in a concentration-dependent manner, and this effect was inhibited by sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP). In the presence of L-arginine, but not D-arginine, IL-1 beta, an inducer of inducible NO synthase, also inhibited AII-induced SMC migration, and this effect was prevented by the NO-synthase inhibitor, N-nitro-L-arginine methyl ester. The effects of NO donors on AII-induced SMC migration were mimicked by 8-bromo-cGMP. Also, the antimigratory effects of SNAP were partially inhibited by LY83583 (an inhibitor of soluble guanylyl cyclase) and by KT5823 (an inhibitor of cGMP-dependent protein kinase). Although 8-bromo-cAMP (cAMP) also mimicked the antimigratory effects of NO donors, the antimigratory effects of SNAP were not altered by 2',5'-dideoxyadenosine (an inhibitor of adenyl cyclase) or by (R)-p-adenosine-3',5'-cyclic phosphorothioate (an inhibitor of the cAMP-dependent protein kinase). Low concentrations of the subtype AT1-receptor antagonist CGP 48933, but not the subtype AT2-receptor antagonist CGP 42112, blocked AII-induced SMC migration. These findings indicate that (a) NO inhibits AII-induced migration of vascular SMCs; (b) the antimigratory effect of NO is mediated in part via a cGMP-dependent mechanism; and (c) AII stimulates SMC migration via an AT1 receptor.

MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate/pharmacology Angiotensin II/antagonists & inhibitors Angiotensin Receptor Antagonists Animals Cell Movement/drug effects Cells, Cultured Male Muscle, Smooth, Vascular/cytology Nitric Oxide/physiology Nitroprusside/pharmacology Nucleotides, Cyclic/physiology Rats Rats, Sprague-Dawley Receptors, Angiotensin/physiology
Chemicals
Angiotensin Receptor Antagonists Nucleotides, Cyclic Receptors, Angiotensin Angiotensin II Nitroprusside 8-Bromo Cyclic Adenosine Monophosphate Nitric Oxide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dubey R K
Department of Medicine and Research, University Hospitals Basel, Switzerland.
Jackson E K
Lüscher T F
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118014
Published
1995-07-00
Pages
141-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC185182
Subset
IM
Grants
NHLBI NIH HHS · HL-14192 · United States
NHLBI NIH HHS · HL-35909 · United States
External Links
PubMed source DOI: 10.1172/JCI118014 PMC Full Text View journal details
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