Interaction of atrial natriuretic polypeptide and angiotensin II on protooncogene expression and vascular cell growth

Hiroshi Itoh, Richard E. Pratt, Victor J. Dzau

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Abstract

Recent evidence suggests that vasoconstrictive substances, including angiotensin II (Ang II), may function as a vascular smooth muscle growth promoting substance and may contribute to vascular hypertrophy in hypertension. Atrial natriuretic polypeptide (ANP) is known to be a physiological antagonist to Ang II in blood pressure and fluid homeostasis. Moreover, we have demonstrated that ANP can attenuate Ang II's action on vascular hypertrophy. In this study, we investigated the potential molecular mechanisms for the interaction of ANP and Ang II on vascular cell growth. Ang II dose-dependently induced RNA synthesis in post confluent cultured rat aortic smooth muscle (RASM) cells. ANP (10-7M) inhibited the hypertrophic effect of Ang II at the concentration of 10-10 - 10-8M but exerted no effect on the action of higher doses (10-7 - 10-6M) of Ang II. Ang II (10-9 - 10-8M) and a protein kinase C activator, phorbol 12-myristate 13-acetate (PMA, 10-8M) rapidly induced c-fos as well as c-Jun and Jun-B mRNA expression in RASM cells. ANP (10-7M) itself had no apparent effect on the expression of these protooncogenes. Furthermore, ANP did not inhibit the induction of these protooncogenes by Ang II or PMA. Paradoxically, ANP (10-7M) significantly enhanced c-fos mRNA expression induced by Ang II and PMA. However, the chloramphenicol acetyl transferase (CAT) assay using a CAT expression vector containing the AP-1 binding element showed that ANP had no effect on the basal and PMA-stimulated AP-1 activity in transfected RASM cells. We conclude, therefore, that the inhibitory effect of ANP on the growth of vascular smooth muscle cells in vitro does not occur through the regulation of these protooncogene expressions.

Original languageEnglish
Pages (from-to)1601-1609
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume176
Issue number3
DOIs
Publication statusPublished - 1991 May 15

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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