Affiliation:
1. From the Departments of Internal Medicine (S.P.D., C.M.L., F.M.F.), Pathology (G.L.B.), and Pharmacology (F.M.F.), Cardiovascular Center, University of Iowa Carver College of Medicine Iowa City.
Abstract
Background and Purpose—
Although the incidence of type II diabetes is increasing, very little is known regarding vascular responses in the cerebral circulation in this disease. The goals of this study were to examine the role of superoxide in impaired endothelium-dependent responses and to examine the influence of Rho-kinase on vascular tone in the cerebral microcirculation in type II diabetes.
Methods—
Diameter of cerebral arterioles (29±1 μm; mean±SE) was measured in vivo using a cranial window in anesthetized
db/db
and control mice.
Results—
Dilatation of cerebral arterioles in response to acetylcholine (ACh; 1 and 10 μmol/L), but not to nitroprusside, was markedly reduced in
db/db
mice (eg, 10 μmol/L ACh produced 29±1% and 9±1% in control and
db/db
mice, respectively). Superoxide levels were increased (
P
<0.05) in cerebral arterioles from
db/db
mice (n=6) compared with controls (n=6). Vasodilatation to ACh in
db/db
mice was restored to normal by polyethylene glycol-superoxide dismutase (100 U/mL). Y-27632 (1 to 100 μmol/L; a Rho-kinase inhibitor) produced modest vasodilatation in control mice but much greater responses in
db/db
mice.
N
G
-nitro-
l
-arginine (100 μmol/L; an inhibitor of NO synthase) significantly enhanced Y-27632–induced dilatation in control mice to similar levels as observed in
db/db
mice.
Conclusions—
These findings provide the first evidence for superoxide-mediated impairment of endothelium-dependent responses of cerebral vessels in any model of type II diabetes. In addition, the influence of Rho-kinase on resting tone appears to be selectively enhanced in the cerebral microcirculation in this genetic model of type II diabetes.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Advanced and Specialised Nursing,Cardiology and Cardiovascular Medicine,Clinical Neurology
Cited by
95 articles.
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