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PMID: 2173726 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells.

The Journal of clinical investigation ·Vol. 86 ·No. 5 ·1990-11-00 ·Pages 1690-7

Itoh H, Pratt RE, Dzau VJ

Abstract

Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. Recent evidence suggests that vasoconstrictive substances, such as angiotensin II (AII), may function as a vascular smooth muscle growth promoting substance. To explore the role of the counterregulatory hormone, atrial natriuretic polypeptide (ANP) in this process, we examined the effect of ANP (alpha-rat ANP [1-28]) on the growth characteristics of cultured rat aortic smooth muscle (RASM) cells. ANP (10(-7) M) significantly suppressed the proliferative effect of 1% and 5% serum as measured by 3H-thymidine incorporation and cell number, confirming ANP as an antimitogenic factor. In quiescent RASM cells, ANP (10(-7), 10(-6) M) significantly suppressed the basal incorporations of 3H-uridine and leucine by 50 and 30%, respectively. ANP (10(-7), 10(-6) M) also suppressed AII-induced RNA and protein syntheses (by 30-40%) with the concomitant reduction of the cell size. Furthermore, ANP also significantly attenuated the increase of 3H-uridine and leucine incorporations caused by transforming growth factor-beta (4 x 10(-11), 4 x 10(-10) M), a potent hypertrophic factor. These results indicate that ANP possesses an antihypertrophic action on vascular smooth muscle cells. Down-regulation of protein kinase C by 24-h treatment with phorbol 12,13-dibutyrate did not inhibit ANP-induced suppression on 3H-uridine incorporation. Based on the observation that ANP was more potent than a ring-deleted analogue of ANP on inhibiting 3H-uridine incorporation, we conclude that the ANP's inhibitory effect is primarily mediated via the activation of a guanylate cyclase-linked ANP receptor(s). Indeed 8-bromo cGMP mimicked the antihypertrophic action of ANP. Accordingly, we speculate that in addition to its vasorelaxant and natriuretic effects, the antihypertrophic action of ANP observed in the present study may serve as an additional compensatory mechanism of ANP in hypertension.

MeSH Terms
Angiotensin II/pharmacology Animals Aorta Atrial Natriuretic Factor/pharmacology Cell Division Cell Line Cyclic GMP/metabolism Down-Regulation Hypertrophy Muscle, Smooth, Vascular/cytology,drug effects Protein Kinase C/metabolism Rats Receptors, Atrial Natriuretic Factor Receptors, Cell Surface/metabolism Transforming Growth Factor beta/pharmacology
Chemicals
Receptors, Cell Surface Transforming Growth Factor beta Angiotensin II Atrial Natriuretic Factor Protein Kinase C Receptors, Atrial Natriuretic Factor Cyclic GMP
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Itoh H
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Pratt R E
Dzau V J
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42 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114893
Published
1990-11-00
Pages
1690-7
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC296921
Subset
IM
Grants
NHLBI NIH HHS · HL19259 · United States
NHLBI NIH HHS · HL35610 · United States
NHLBI NIH HHS · HL35792 · United States
External Links
PubMed source DOI: 10.1172/JCI114893 PMC Full Text View journal details
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