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constriction is enhanced in proximal middle cerebral arteries from STZ-induced
diabetic female SD rat [
113
]. Matsumoto et al. indicated that endothelin-1 induced
contraction was enhanced in basilar arteries from STZ induced male Wistar rats
[
114
]. In skeletal (gracilis) muscle 1st order arterioles from diabetic Wistar rats,
myogenic response was also increased in perfusion pressure (50-140 mmHg) [
115
].
4.1.3 Type 2 Diabetes Models
Mouse Models of Type 2 Diabetes
The most popular mouse model for type 2 diabetes is db/db mouse, which homo-
zygous for the diabetes spontaneous mutation (Lepr
db
). They become obese
3-4 weeks of age with elevation of plasma insulin and glucose. Interestingly,
myogenic responses for this model are consistently increased or no change
regardless of age and vascular beds. Specifically, in the mesentery arteries, myo-
genic constriction to increased pressure or agonist (phenylephrine) are elevated
regardless of order of the artery, age and methods used (isometric versus isobaric)
[
116
-
119
]. In addition, stepwise increases in intraluminal pressure (20-120 mmHg)
elicited a greater constriction in isolated, pressurized skeletal (gracilis) muscle
arterioles from db/db mice [
120
,
121
]. For coronary vasculatures, Belmadani et al.
showed that pressure-induced myogenic tone was increased in coronary artery from
diabetic mice [
116
], while in the coronary septal arteries, myogenic tone was not
different in WT mice and db/db mice [
122
].
Rat Models of Type 2 Diabetes
The most popular rat models for type2 diabetes in the myogenic responses are the
Goto-Kakizaki (GK) and BBZDR/Wor rats. The GK rat is a non-obese Wistar sub-
strain, which develops characteristics of type 2 diabetes including fasting hyper-
glycemia and impaired production of insulin to glucose at 14-16 weeks of age
[
123
-
125
]. In the cerebral artery from this model, it seemed that duration of dia-
betes is a major determinant in altering myogenic responses. At relatively young
diabetes, myogenic tone was increased in the middle cerebral arteries from 10 to
12-week diabetic animals [
126
,
127
], while cerebral arteries from 18 to 22-week-
old GK developed less tone than control rats [
126
-
128
], suggesting that longer
duration of diabetes may cause impairment of myogenic constriction in the cerebral
arteries from this diabetic animal model. However, 18-week GK rats displayed
hypersensitivity to endothelin-1 in the basilar artery with isometric method [
129
].
In the mesenteric arteries, microvascular tone at 60 and 80 mmHg intraluminal
pressure was increased in 18-weeks diabetes, and Ishida et al. indicated that iso-
metric vasoconstriction to prostaglandin E2 from 37 to 44-week-old GK rat was
increased in the endothelial denuded mesenteric artery rings [
130
]. In contrast to
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