Upregulation of c-Src-dependent non-genomic signaling by aldosterone in vascular smooth muscle cells from spontaneously hypertensive rats (2005)
- Authors:
- Autor USP: PASSAGLIA, RITA DE CASSIA ALEIXO TOSTES - ICB
- Unidade: ICB
- Assunto: FARMACOLOGIA
- Language: Português
- Abstract: Objetivo: Aldosterone plays an important role in the pathogenesis of hypertension. We previously demonstrated that non-genomic signaling by aldosterone occurs through c-Src-dependent pathways. In addition, endothelin-1 (ET-1) has been implicated as a mediator of aldosteroneinduced oxidative stress and vascular remodeling. We tested the hypothesis that aldosteroneinduced activation of vascular MAP kinases, collagen synthesis and NADPH oxidase via c-Srcdependent mechanisms is increased in cultured SHR vascular smooth muscle cells (VSMCs). We further investigated the role of ET-1 receptors in these processes. Métodos e Resultados: Time-course c-Src phosphorylation by aldosterone was shifted to the right in VSMCs from SHR (15 min: SHR - 157±5 vs. WKY - 111±6, arbitrary units). Aldosterone rapidly increased phosphorylation of p38MAP kinase and ERK1/2 with significantly greater effects in SHR vs WKY cells. Aldosterone increased NADPH oxidase activity with significantly greater responses (% of basal) in VSMC from SHR vs WKY (60 minutes: 277±37 vs. 170±15, p<0.05). These events were associated with enhanced [3H]proline incorporation (collagen synthesis index, % of basal) in SHR (137±5%) vs. WKY (119±4%, p<0.05). Increase in NADPH oxidase activity, collagen synthesis, c-Src and MAP kinase phosphorylation induced by aldosterone were significantly reduced by eplerenone (selective mineralocorticoid receptor blocker), PP2 (selective Src inhibitor), bosentan (ETA/ETB receptorblocker) and BMS182874 (ETA receptor blocker) (p<0.05). Conclusões: In conclusion, non-genomic signaling by aldosterone, mediated through c-Src is increased in SHR VSMCs. Upregulation of c-Src pathway may play a role in aldosterone-stimulated collagen synthesis and vascular fibrosis in hypertension. Cross-talk through ETA receptors may be important in these events
- Imprenta:
- Publisher: Federação de Sociedades de Biologia Experimental
- Publisher place: Águas de Lindóia, São Paulo
- Date published: 2005
- Source:
- Título do periódico: Resumos
- Conference titles: Reunião Anual da Federação de Sociedades de Biologia Experimental, FeSBE
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ABNT
MONTEZANO, A. C. et al. Upregulation of c-Src-dependent non-genomic signaling by aldosterone in vascular smooth muscle cells from spontaneously hypertensive rats. 2005, Anais.. Águas de Lindóia, São Paulo: Federação de Sociedades de Biologia Experimental, 2005. . Acesso em: 18 abr. 2024. -
APA
Montezano, A. C., Callera, G. E., Yogi, A., Passaglia, R. de C. A. T., Schiffrin, E. L., & Touyz, R. M. (2005). Upregulation of c-Src-dependent non-genomic signaling by aldosterone in vascular smooth muscle cells from spontaneously hypertensive rats. In Resumos. Águas de Lindóia, São Paulo: Federação de Sociedades de Biologia Experimental. -
NLM
Montezano AC, Callera GE, Yogi A, Passaglia R de CAT, Schiffrin EL, Touyz RM. Upregulation of c-Src-dependent non-genomic signaling by aldosterone in vascular smooth muscle cells from spontaneously hypertensive rats. Resumos. 2005 ;[citado 2024 abr. 18 ] -
Vancouver
Montezano AC, Callera GE, Yogi A, Passaglia R de CAT, Schiffrin EL, Touyz RM. Upregulation of c-Src-dependent non-genomic signaling by aldosterone in vascular smooth muscle cells from spontaneously hypertensive rats. Resumos. 2005 ;[citado 2024 abr. 18 ] - ET-1-induced oxidative stress in doca-salt hypertension involves NAD(P)H oxidase-independent mechanisms
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