Impaired endothelium-dependent responses and enhanced influence of rho-kinase in cerebral arterioles in type II diabetes

• Published in: Stroke (1970) 2005-02, Vol.36 (2), p.342-347
• Main Authors: DIDION, Sean P, LYNCH, Cynthia M, BAUMBACH, Gary L, FARACI, Frank M
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Amides - pharmacology; Animals; Biological and medical sciences; Blood Glucose - metabolism; Body Weight; Cerebral Arteries - pathology; Cerebrovascular Circulation; Diabetes Mellitus, Type 2 - pathology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Enzyme Inhibitors - pharmacology; Errors of metabolism; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Intracellular Signaling Peptides and Proteins; Lipids (lysosomal enzyme disorders, storage diseases); Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Nervous system (semeiology, syndromes); Neurology; Nitric Oxide Synthase - chemistry; Nitroarginine - chemistry; Nitroarginine - pharmacology; Nitroprusside - pharmacology; Polyethylene Glycols - metabolism; Protein-Serine-Threonine Kinases - physiology; Pyridines - pharmacology; Reactive Oxygen Species; rho-Associated Kinases; Superoxide Dismutase - metabolism; Superoxides - chemistry; Superoxides - metabolism; Vascular diseases and vascular malformations of the nervous system; Vasoconstrictor Agents - pharmacology; Vasodilation; Vasodilator Agents - pharmacology
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.0000152952.42730.92

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. Diameter of cerebral arterioles (29+/-1 microm; mean+/-SE) was measured in vivo using a cranial window in anesthetized db/db and control mice. Dilatation of cerebral arterioles in response to acetylcholine (ACh; 1 and 10 micromol/L), but not to nitroprusside, was markedly reduced in db/db mice (eg, 10 micromol/L ACh produced 29+/-1% and 9+/-1% in control and db/db mice, respectively). Superoxide levels were increased (P