TY - JOUR
T1 - Interaction of atrial natriuretic polypeptide and angiotensin II on protooncogene expression and vascular cell growth
AU - Itoh, Hiroshi
AU - Pratt, Richard E.
AU - Dzau, Victor J.
N1 - Funding Information:
This work is supported by NM grants HL35610, HL35252, HL42663, and the University of California Tobacco Related Disease Program lRT215. Hiroshi Itoh is the recipient of Bristol Meyer-Squibb Japan-Stanford Fellowship Award.
PY - 1991/5/15
Y1 - 1991/5/15
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-291X(91)90471-I
DO - 10.1016/0006-291X(91)90471-I
M3 - Article
C2 - 1828153
AN - SCOPUS:0025861890
SN - 0006-291X
VL - 176
SP - 1601
EP - 1609
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -