TY - CONF

T1 - Synergism of diabetic and inflammatory culture conditions on reactivity of isolated small arteries

AU - Blædel, Martin Mads

AU - Boonen, Harrie C.M.

AU - Sams Nielsen, Anette

AU - Sheykhzade, Majid

PY - 2011/1/19

Y1 - 2011/1/19

N2 - Background: Cardiovascular disease (CVD) is the manifestation of atherosclerosis, which has been linked to obesity, the metabolic syndrome (MS) and overt type 2 diabetes (T2DM). Vascular dysfunction has been proposed to precede atherosclerosis, and in addition, a correlation between vascular dysfunction and local vascular inflammation has been suggested. Aim: This study addresses the involvement of vascular risk factors of MS and T2DM such as elevated glucose, increased insulin levels, as well as selected cytokines on vascular contractile function. Methods: Small mesenteric resistance arteries isolated from 8 week old male SD rats were cultured for 21 hours in Endothelial Basal Medium (EBM-2) in petri dishes and in the absence or presence of either 30 mM D-glucose, 100 nM insulin, 100 ng/mL TNFa or any combination of these. Contractile reactivity of normalised arteries was then determined by wire myography as a response to cumulatively increasing concentrations of noradrenaline (NA). Results: 21 hour culture of isolated mesenteric arteries significantly reduced the arteries maximal high potassium-induced contractile reactivity and increased the contractility to noradrenaline slightly. Arteries that had been incubated in the presence of either D-glucose, insulin, or TNFa alone, displayed unchanged sensitivity and max. responses to NA as compared to control conditions (21 hour incubation in EBM-2 only). However, when arteries were incubated in combinations of glucose, insulin or TNF-a, the NA-induced max. responses and sensitivity significantly increased. Conclusion: These results suggest that the continuous presence of inflammatory cytokines may significantly enhance hyperglycaemia and hyperinsulinaemia-induced changes in vascular reactivity of cultured small arteries. An increased vascular inflammatory status might therefore be pivotal for the development of CVD in diabetes.

AB - Background: Cardiovascular disease (CVD) is the manifestation of atherosclerosis, which has been linked to obesity, the metabolic syndrome (MS) and overt type 2 diabetes (T2DM). Vascular dysfunction has been proposed to precede atherosclerosis, and in addition, a correlation between vascular dysfunction and local vascular inflammation has been suggested. Aim: This study addresses the involvement of vascular risk factors of MS and T2DM such as elevated glucose, increased insulin levels, as well as selected cytokines on vascular contractile function. Methods: Small mesenteric resistance arteries isolated from 8 week old male SD rats were cultured for 21 hours in Endothelial Basal Medium (EBM-2) in petri dishes and in the absence or presence of either 30 mM D-glucose, 100 nM insulin, 100 ng/mL TNFa or any combination of these. Contractile reactivity of normalised arteries was then determined by wire myography as a response to cumulatively increasing concentrations of noradrenaline (NA). Results: 21 hour culture of isolated mesenteric arteries significantly reduced the arteries maximal high potassium-induced contractile reactivity and increased the contractility to noradrenaline slightly. Arteries that had been incubated in the presence of either D-glucose, insulin, or TNFa alone, displayed unchanged sensitivity and max. responses to NA as compared to control conditions (21 hour incubation in EBM-2 only). However, when arteries were incubated in combinations of glucose, insulin or TNF-a, the NA-induced max. responses and sensitivity significantly increased. Conclusion: These results suggest that the continuous presence of inflammatory cytokines may significantly enhance hyperglycaemia and hyperinsulinaemia-induced changes in vascular reactivity of cultured small arteries. An increased vascular inflammatory status might therefore be pivotal for the development of CVD in diabetes.

M3 - Poster

T2 - 3rd Annual meeting Danish Society for Pharmacology

Y2 - 19 January 2011 through 19 January 2011

ER -