08:00 EDT 16th October 2015 | BioPortfolio


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 to 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 was determined at 7-8, 12-13 and 16-17 weeks 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 reactivity (acetylcholine), elevated myogenic properties, structural narrowing and wall stiffening versus LZR. Anti-hypertensive therapy starting at 7-8 weeks of age (e.g., captopril or hydralazine) blunted the progression of arterial stiffening compared to OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, captopril) improved NO bioavailability and vascular reactivity compared to OZR controls with mixed impacts on structural remodeling. These data identify specific functional and structural cerebral adaptions 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.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Heart and circulatory physiology
ISSN: 1522-1539
Pages: ajpheart.00691.2015


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