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P20 Study of insulin cardiovascular resistance in an animal model of childhood obesity by over-feeding during lactation
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  1. L Guerra- Menéndez1,
  2. S Amor2,
  3. B Martín-Carro2,
  4. D González Hedström2,
  5. A Tejera2,
  6. B Oltra1,
  7. R Arriazu1,
  8. G Diéguez1,
  9. AL García-Villalón2,
  10. M Granado2
  1. 1Departamento de Fisiología, Facultad de Medicina, Universidad San Pablo CEU
  2. 2Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid

Abstract

Childhood obesity is a pandemic that has become one of the major public health problems of the 21st century. The aim of this work was to analyse cardiovascular insulin sensitivity in an experimental model of early overnutrition.

Male 21-day-old Sprague-Dawley rats were used. On the day of weaning offspring were weighed and sacrificed by decapitation. Hearts were mounted in a Langendorff system whereby increasing doses of insulin were administered (10–10–10–7M). In addition, 2mm rings of aorta were mounted in an organ bath and precontracted with phenylephrine (10–7.5 M). Changes in isometric tension were recorded after addition of cumulative insulin doses (10–8–10–5.5 M) in the presence or absence of L-NAME (10–4M).

On the day of weaning, the body weight of offspring raised in reduced litters was significantly higher than that of control pups. Hearts from overfed offspring showed lower contractility (dp/dt) both at baseline and in response to increasing doses of insulin than controls. Insulin induced greater vasodilation of the coronary arteries in the hearts of offspring from C12 than in offspring from C3. Similarly, the aortic rings from overfed offspring showed decreased insulin relaxation in the aortic rings compared to controls, an effect that was blocked by the preincubation of the arterial rings with the N-oxide synthase inhibitor L-NAME.

Overfeeding during lactation in rats is associated with cardiovascular insulin resistance both in the heart and in the aorta. This fact could be associated, at least in part, with the higher incidence of cardiovascular diseases in individuals with long-standing obesity.

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