RGD Reference Report - c-Src-dependent nongenomic signaling responses to aldosterone are increased in vascular myocytes from spontaneously hypertensive rats. - Rat Genome Database

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c-Src-dependent nongenomic signaling responses to aldosterone are increased in vascular myocytes from spontaneously hypertensive rats.

Authors: Callera, GE  Montezano, AC  Yogi, A  Tostes, RC  He, Y  Schiffrin, EL  Touyz, RM 
Citation: Callera GE, etal., Hypertension. 2005 Oct;46(4):1032-8. Epub 2005 Sep 12.
RGD ID: 1601372
Pubmed: PMID:16157790   (View Abstract at PubMed)
DOI: DOI:10.1161/01.HYP.0000176588.51027.35   (Journal Full-text)

Aldosterone plays an important role in the pathogenesis of hypertension. We previously demonstrated that nongenomic signaling by aldosterone in vascular smooth muscle cells occurs through c-Src-dependent pathways. Here we tested the hypothesis that upregulation of c-Src by aldosterone plays a role in increased mitogen-activated protein (MAP) kinase activation, [3H]-proline incorporation, and NADPH-driven generation of reactive oxygen species, thereby inducing cell growth, collagen production, and inflammation, respectively, in vascular smooth muscle cells from spontaneously hypertensive rats. The time course of c-Src phosphorylation by aldosterone was shifted to the left in vascular myocytes from hypertensive animals. Aldosterone rapidly increased phosphorylation of p38 MAP kinase and extracellular signal-regulated kinase with significantly greater effects in cells from spontaneously hypertensive rats versus control cells (P<0.05). Aldosterone increased NADPH oxidase activity with significantly greater responses in vascular smooth muscle cells from hypertensive animals (P<0.05). These events were associated with enhanced [3H]proline incorporation (index of collagen synthesis) in cells from spontaneously hypertensive rats (P<0.05). The NADPH oxidase activity increase, collagen synthesis, c-Src, and MAP kinase phosphorylation induced by aldosterone were significantly reduced by eplerenone (selective mineralocorticoid receptor blocker) and PP2 (selective c-Src inhibitor). In conclusion, nongenomic signaling by exogenous aldosterone, mediated through c-Src, is increased in vascular smooth muscle cells from spontaneously hypertensive rats. Upregulation of c-Src signaling may be important in the profibrotic and proinflammatory actions of aldosterone in this genetic model of hypertension.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOSrc (Rattus norvegicus)1601372; 1601372 RGD 
hypertension  IDA 1601372 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to mineralocorticoid  IEP 1601372 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Src  (SRC proto-oncogene, non-receptor tyrosine kinase)

Genes (Mus musculus)
Src  (Rous sarcoma oncogene)

Genes (Homo sapiens)
SRC  (SRC proto-oncogene, non-receptor tyrosine kinase)


Additional Information