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1 Institute of Physiology and Biophysics, Water and Salt Research Center, University of Aarhus, Ole Worms Alle, build. 1160, Aarhus, DK-8000, Denmark,
2 Medical Department M, Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus, DK-8000, Denmark
ABSTRACT
Here we studied isolated small cerebral (CerSA) and coronary septal arteries (CorSA) from 9 control Wistar rats (CW-) to responses in 10 spontaneously diabetic Goto-Kakizaki (GK-) rat, a model of lean type 2 diabetes. CerSA and CorSA were investigated under isobaric conditions while changes in [Ca2+]i were measured simultaneously. CerSA from GK-rats developed significantly less myogenic tone than CerSA from CW at 100 mmHg, 10.6 ± 3%, 27.5 ± 3%, (p<0.001), GK-rats and CW-rats, respectively. There were no differences in [Ca2+]i. However, after exposure to 10µM of the Rho A kinase inhibitor Fasudil the myogenic response was similar in the two groups, 9 ± 4 %, 14 ± 2%, (p=0.3), GK-rats and CW-rats, respectively. Also CorSA from the GK-rats developed significantly less myogenic tone than CorSA from CW at 100 mmHg, 9 ± 3%, 20 ± 3%, (p<0.001), GK-rats and CW-rats, respectively. As in the CerSA this was not associated with differences in [Ca2+]i
In the CerSA there were no differences in the response to 1 µM U46619, nor were there any differences in CorSA to 3 µM prostaglandin F2
. In CorSA the sensitivity and maximal response to acetylcholine was similar in arteries from the two groups.
These data suggest that the myogenic contraction in both CerSA and CorSA is decreased due to impaired calcium sensitivity. Furthermore, we did not find any evidence of endothelial dysfunction in the GK-rat despite the presence of type 2 diabetes in the GK-rat.
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