title: Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats.
abstract: The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7-8, 12-13, and 16-17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7-8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Brooks
authors.affiliation: Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
authors.forename: Evan
authors.initials: E
authors.lastname: DeVallance
authors.affiliation: Department of Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: d'Audiffret
authors.affiliation: Center for Basic and Translational Stroke Research, West Virginia University Health Sciences Center, Morgantown, West Virginia; and Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia jefrisbee@hsc.wvu.edu.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Frisbee
authors.affiliation: Department of Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Tabone
authors.affiliation: Department of Family Medicine, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Shrader
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Basic and Translational Stroke Research, West Virginia University Health Sciences Center, Morgantown, West Virginia; and Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
authors.forename: Jefferson C
authors.initials: JC
authors.lastname: Frisbee
authors.affiliation: Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Basic and Translational Stroke Research, West Virginia University Health Sciences Center, Morgantown, West Virginia; and Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Chantler
mesh_terms: D000367:Age Factors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D018384:Oxidative Stress; D011924:Rats, Zucker; D066253:Vascular Remodeling; D014655:Vascular Resistance / Q000187:drug effects; D059289:Vascular Stiffness; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D000975:Antioxidants; D018836:Inflammation Mediators; D014665:Vasodilator Agents; D009569:Nitric Oxide
keywords: arterial stiffness; cerebrovascular remodeling; metabolic syndrome; reactive oxygen species