Artículo
Central insulin–angiotensin II interaction in blood pressure regulation in fructose overloaded rats
Mayer, Marcos Alejandro
; Höcht, Christian; Giani, Jorge Fernando
; Muñoz, Marina Cecilia
; Carranza, A.; Taira, Carlos Alberto
; Dominici, Fernando Pablo
; Puyó, Ana María; Fernández, B. E.
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Fecha de publicación:
08/2013
Editorial:
Elsevier Science
Revista:
Regulatory Peptides
ISSN:
0167-0115
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The aim of the present study was to determine if insulin is able to modulate the pressor response to intracerebroventricularly administered angiotensin II in insulin resistant fructose overloaded rats. Male Sprague-Dawley rats were divided into two groups: 1) Control group (C) with tap water to drink for 6 weeks (n = 36); and 2) fructose treated (F), with fructose solution (10% w/v) to drink for 6 weeks (n = 36). On the day of the experiment, anesthetized male C and F rats were intracerebroventricularly infused with insulin (12 mU/h, n = 15) or Ringer's solution as vehicle (n = 15) for 2 h. Immediately, changes in mean arterial pressure (MAP) in response to an intracerebroventricular subpressor dose of angiotensin II (5 pmol, n = 10) or vehicle (n = 5) were measured for 10 min. Then, hypothalami were removed and Akt and ERK1/2 phosphorylation levels were determined. In a subset of C (n = 10) and F (n = 20) animals, PD98059 (p44/42 MAPK inhibitor) or vehicle was administered intracerebroventricularly at a flow rate of 5 μl/min for 1 min. Ten minutes later, insulin (12 mU/h, n = 5 for each group) or vehicle (Ringer's solution, only in the F group, n = 5) was perfused for 2 h at a flow rate of 4 μl/h, and cardiovascular parameters were measured every 15 min. Immediately, changes in MAP and HR in response to a subpressor dose of Ang II (5 pmol/2 μl) were evaluated for 10 min (n = 5 for each group). In other subset of animals (n = 6 for each group), AT1 and AT2 hypothalamic receptor levels were measured by Western blotting. Intracerebroventricular insulin pre-treatment increased the pressor response to angiotensin II in C rats. In F rats (with or without insulin pretreatment), the pressor response to angiotensin II was higher than that in vehicle pre-treated C animals, but similar to that observed in C after insulin infusion. In C rats phospho-ERK 1/2 hypothalamic levels significantly increased after angiotensin II injection in insulin pretreated animals compared to vehicle pre-treated rats, suggesting that MAPK activation might be involved in insulin potentiation of blood pressure response to angiotensin II in the brain. Phospho-ERK 1/2 hypothalamic levels were significantly increased in vehicle treated F rats compared to C, suggesting that basal MAPK activation might play a role in the enhanced response to angiotensin II observed in these animals. Finally, in F rats, either after vehicle or insulin infusion, angiotensin II injection was associated with a similar increase in phospho-ERK 1/2 hypothalamic levels, comparable to that observed after angiotensin II injection in insulin pre-treated C animals. ERK 1/2 blockade significantly reduced MAP in F rats compared to C. Moreover, ERK 1/2 inhibition completely abolished the Ang II pressor response in F rats and in insulin pre-treated C animals. All these findings suggest that insulin–angiotensin II interaction at hypothalamic level might be involved in the increase in blood pressure observed in the insulin resistant state.
Palabras clave:
Hypertension
,
Fructose
,
Angiotensin
,
Insulin
,
Hypothalamus
,
Blood Pressure
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Licencia
Identificadores
Colecciones
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
Mayer, Marcos Alejandro; Höcht, Christian; Giani, Jorge Fernando; Muñoz, Marina Cecilia; Carranza, A.; et al.; Central insulin–angiotensin II interaction in blood pressure regulation in fructose overloaded rats; Elsevier Science; Regulatory Peptides; 185; 8-2013; 37-43
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