+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Angiotensin-(1-7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity



Angiotensin-(1-7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity



Experimental Physiology 93(5): 570-578



Angiotensin (ANG) II contributes to cardiac remodelling by inducing the activation of several signalling molecules, including ERK1/2, Rho kinase and members of the STAT family of proteins. Angiotensin-(1-7) is produced in the heart and inhibits the proliferative actions of ANG II, although the mechanisms of this inhibition are poorly understood. Accordingly, in the present study we examined whether ANG-(1-7) affects the ANG II-mediated activation of ERK1/2 and Rho kinase, STAT3 and STAT5a/b in rat heart in vivo. We hypothesized that ANG-(1-7) inhibits these growth-promoting pathways, counterbalancing the trophic action of ANG II. Solutions of normal saline (0.9% NaCl) containing ANG II (8 pmol kg(-1)) plus ANG-(1-7) in increasing doses (from 0.08 to 800 pmol kg(-1)) were administered via the inferior vena cava to anaesthetized male Sprague-Dawley rats. After 5 min, hearts were removed and ERK1/2, Rho kinase, STAT3 and STAT5a/b phosphorylation was determined by Western blotting using phosphospecific antibodies. Angiotensin II stimulated ERK1/2 and Rho kinase phosphorylation (2.3 +/- 0.2- and 2.1 +/- 0.2-fold increase over basal values, respectively), while ANG-(1-7) was without effect. The ANG II-mediated phosphorylation of ERK1/2 and Rho kinase was prevented in a dose-dependent manner by ANG-(1-7) and disappeared in the presence of the Mas receptor antagonist D-Ala(7)-ANG-(1-7). Both ANG II and ANG-(1-7) increased STAT3 and STAT5a/b phosphorylation to a similar extent (130-140% increase). The ANG-(1-7)-stimulated STAT phosphorylation was blocked by the AT(1) receptor antagonist losartan and not by D-Ala(7)-ANG-(1-7). Our results show a dual action of ANG-(1-7), that is, a stimulatory effect on STAT3 and 5a/b phosphorylation through AT(1) receptors and a blocking action on ANG II-stimulated ERK1/2 and Rho kinase phosphorylation through Mas receptor activation. The latter effect could be representative of a mechanism for a protective role of ANG-(1-7) in the heart by counteracting the effects of locally generated ANG II.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 030084989

Download citation: RISBibTeXText

PMID: 18448663

DOI: 10.1113/expphysiol.2007.014269


Related references

Role of IκB kinase-β in the growth-promoting effects of angiotensin II in vitro and in vivo. Arteriosclerosis, Thrombosis, and Vascular Biology 33(12): 2850-2857, 2014

Ethanol inhibition of angiotensin II-stimulated Tyr705 and Ser727 STAT3 phosphorylation in cultured rat hepatocytes: relevance to activation of p42/44 mitogen-activated protein kinase. Alcohol 42(5): 397-406, 2008

Dual pathways for nuclear factor kappaB activation by angiotensin II in vascular smooth muscle: phosphorylation of p65 by IkappaB kinase and ribosomal kinase. Circulation Research 97(10): 975-982, 2005

Angiotensin II-stimulated collagen gel contraction by heart fibroblasts: role of the AT1 receptor and tyrosine kinase activity. Journal of Cellular Physiology 177(2): 224-231, 1998

Epidermal growth factor stimulated tyrosine kinase activity in plasma membranes from as 30d rat hepatoma the possible role of lonidamine in inhibiting growth factors receptors phosphorylation. Puett, D Et Al (Ed ) Icsu Short Reports, Vol 4 Advances in Gene Technology: Molecular Biology Of The Endocrine System; 18th Miami Winter Symposium, Miami, Fla , Usa, Feb 3-7, Xxv+402p Cambridge University Press: New York, N Y , Usa; Cambridge, England Illus 198-199, 1986

Differential pathways of angiotensin II-induced extracellularly regulated kinase 1/2 phosphorylation in specific cell types: role of heparin-binding epidermal growth factor. Molecular Endocrinology 18(8): 2035-2048, 2004

Release of active transforming growth factor-beta1 is stimulated by angiotensin II through both PI-3 kinase and MAP kinase pathways in kidney mesangial cells. Journal of the American Society of Nephrology 12(Program and Abstract Issue): 571A, 2001

A novel role of angiotensin II in epidermal cell lineage determination: Angiotensin II promotes the differentiation of mesenchymal stem cells into keratinocytes through the p38 MAPK, JNK and JAK2 signalling pathways. Experimental Dermatology 2018, 2018

Role of STAT3 in angiotensin II-induced hypertension and cardiac remodeling revealed by mice lacking STAT3 serine 727 phosphorylation. Hypertension Research 36(6): 496-503, 2013

Angiotensin-(1-7) enhances angiotensin II induced phosphorylation of ERK1/2 in mouse bone marrow-derived dendritic cells. Molecular Immunology 46(3): 355-361, 2008

Angiotensin-(1-7) improves cardiac remodeling and inhibits growth-promoting pathways in the heart of fructose-fed rats. American Journal of Physiology. Heart and Circulatory Physiology 298(3): H1003-H1013, 2010

Angiotensin II-Stimulated Site Specific Phosphorylation of Git1 Determines the Relative Activation of PLCgamma and ERK1/2. Circulation 102(18 Supplement): II-15, October 31, 2000

Angiotensin-(1-7) attenuates high glucose-induced proximal tubular epithelial-to-mesenchymal transition via inhibiting ERK1/2 and p38 phosphorylation. Life Sciences 90(11-12): 454-462, 2012

Angiotensin-(1 7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: role of the AT1 and Mas receptors. American Journal of Physiology. Heart and Circulatory Physiology 293(2): H1154-H1163, 2007

Identification of metabolic pathways of brain angiotensin II and angiotensin III: predominant role of angiotensin III in the control of vasopressin secretion. Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales 192(4): 607-618, 1998