IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Centrally Administered Insulin Potentiates the Pressor Response To Angiotensin II By Mapk Activation in Rats
Autor/es:
PUYÓ, A; MAYER, MA; GIANI, JF; HÖCHT, C; MUÑOZ, MC; DOMINICI, FP; FERNÁNDEZ, BE; TAIRA, C
Lugar:
Oslo, Noruega
Reunión:
Congreso; 20th European Meeting of Hypertension; 2010
Institución organizadora:
European Society of Hypertension
Resumen:
actions at central level. As insulin and angiotensin II (Ang II) exert some effects at hypothalamic level by MAPK intracellular pathway activation, we evaluated if insulin modifies the central pressor response to Ang II in control (C) and insulin-resistant rats. Methods: Two groups of male Sprague-Dawley rats were studied: C: tap water; fructose (F)-treated: F solution (10% w/v) to drink for 6 weeks (n¼20). A cannulae was inserted in one carotid artery to measure mean arterial pressure (MAP; mmHg). Vehicle or insulin (12 mU/h) was perfused intracerebroventricularly. Changes in MAP were evaluated in response to Ang II 5 pmol. Afterwards, hypothalami were removed to determine ERK1/2 phosphorylation levels.Two groups of male Sprague-Dawley rats were studied: C: tap water; fructose (F)-treated: F solution (10% w/v) to drink for 6 weeks (n¼20). A cannulae was inserted in one carotid artery to measure mean arterial pressure (MAP; mmHg). Vehicle or insulin (12 mU/h) was perfused intracerebroventricularly. Changes in MAP were evaluated in response to Ang II 5 pmol. Afterwards, hypothalami were removed to determine ERK1/2 phosphorylation levels.¼20). A cannulae was inserted in one carotid artery to measure mean arterial pressure (MAP; mmHg). Vehicle or insulin (12 mU/h) was perfused intracerebroventricularly. Changes in MAP were evaluated in response to Ang II 5 pmol. Afterwards, hypothalami were removed to determine ERK1/2 phosphorylation levels. Results: MAP basal value was elevated in F rats (903 vs. C: 753, p<0.05). Ang II increased MAP only in insulin pre-treated C animals (dMAP: 6.30.8 vs. vehicle, p<0.01); meanwhile it elevated MAP in a similar manner in insulin and vehicle pre-treated F rats (dMAP: 5.51.1 and 4.01.0 respectively, p<0.01 vs. C vehicle). Basal phospho-ERK 1/2 hypothalamic levels were similar in both groups. In C and F Ang II or insulin infusion increased more than two fold phospho-ERK 1/2 hypothalamic levels (p<0.05 vs. C vehicle). C animals that received insulin infusion followed by Ang II injection presented 4.5 higher values of phospho-ERK 1/ 2 than those receiving vehicle (p<0.01) meanwhile F rats showed 3.5 higher levels (p<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).MAP basal value was elevated in F rats (903 vs. C: 753, p<0.05). Ang II increased MAP only in insulin pre-treated C animals (dMAP: 6.30.8 vs. vehicle, p<0.01); meanwhile it elevated MAP in a similar manner in insulin and vehicle pre-treated F rats (dMAP: 5.51.1 and 4.01.0 respectively, p<0.01 vs. C vehicle). Basal phospho-ERK 1/2 hypothalamic levels were similar in both groups. In C and F Ang II or insulin infusion increased more than two fold phospho-ERK 1/2 hypothalamic levels (p<0.05 vs. C vehicle). C animals that received insulin infusion followed by Ang II injection presented 4.5 higher values of phospho-ERK 1/ 2 than those receiving vehicle (p<0.01) meanwhile F rats showed 3.5 higher levels (p<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).<0.05). Ang II increased MAP only in insulin pre-treated C animals (dMAP: 6.30.8 vs. vehicle, p<0.01); meanwhile it elevated MAP in a similar manner in insulin and vehicle pre-treated F rats (dMAP: 5.51.1 and 4.01.0 respectively, p<0.01 vs. C vehicle). Basal phospho-ERK 1/2 hypothalamic levels were similar in both groups. In C and F Ang II or insulin infusion increased more than two fold phospho-ERK 1/2 hypothalamic levels (p<0.05 vs. C vehicle). C animals that received insulin infusion followed by Ang II injection presented 4.5 higher values of phospho-ERK 1/ 2 than those receiving vehicle (p<0.01) meanwhile F rats showed 3.5 higher levels (p<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).0.8 vs. vehicle, p<0.01); meanwhile it elevated MAP in a similar manner in insulin and vehicle pre-treated F rats (dMAP: 5.51.1 and 4.01.0 respectively, p<0.01 vs. C vehicle). Basal phospho-ERK 1/2 hypothalamic levels were similar in both groups. In C and F Ang II or insulin infusion increased more than two fold phospho-ERK 1/2 hypothalamic levels (p<0.05 vs. C vehicle). C animals that received insulin infusion followed by Ang II injection presented 4.5 higher values of phospho-ERK 1/ 2 than those receiving vehicle (p<0.01) meanwhile F rats showed 3.5 higher levels (p<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).1.1 and 4.01.0 respectively, p<0.01 vs. C vehicle). Basal phospho-ERK 1/2 hypothalamic levels were similar in both groups. In C and F Ang II or insulin infusion increased more than two fold phospho-ERK 1/2 hypothalamic levels (p<0.05 vs. C vehicle). C animals that received insulin infusion followed by Ang II injection presented 4.5 higher values of phospho-ERK 1/ 2 than those receiving vehicle (p<0.01) meanwhile F rats showed 3.5 higher levels (p<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).1.0 respectively, p<0.01 vs. C vehicle). Basal phospho-ERK 1/2 hypothalamic levels were similar in both groups. In C and F Ang II or insulin infusion increased more than two fold phospho-ERK 1/2 hypothalamic levels (p<0.05 vs. C vehicle). C animals that received insulin infusion followed by Ang II injection presented 4.5 higher values of phospho-ERK 1/ 2 than those receiving vehicle (p<0.01) meanwhile F rats showed 3.5 higher levels (p<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).<0.05 vs. C vehicle). C animals that received insulin infusion followed by Ang II injection presented 4.5 higher values of phospho-ERK 1/ 2 than those receiving vehicle (p<0.01) meanwhile F rats showed 3.5 higher levels (p<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).<0.01) meanwhile F rats showed 3.5 higher levels (p<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).<0.05 vs. C vehicle). Both groups increased twice phospho-ERK 1/ 2 than those treated with Ang II without insulin pre-treatment (p<0.05).<0.05). Conclusions: Centrally administered insulin potentiates the pressor effects of Ang II in C rats, suggesting a novel mechanism, involving MAPK activation, by which insulin influences blood pressure control at central level. The existence of a pressor response to Ang II in F rats, and the absence of changes in this response after previous administration of insulin could be due to the chronic hiperinsulinemia present in this modeCentrally administered insulin potentiates the pressor effects of Ang II in C rats, suggesting a novel mechanism, involving MAPK activation, by which insulin influences blood pressure control at central level. The existence of a pressor response to Ang II in F rats, and the absence of changes in this response after previous administration of insulin could be due to the chronic hiperinsulinemia present in this mode