Nusrat Matin1, Paulo W Pires2,3, Hannah Garver2, William F Jackson2, Anne M Dorrance2. 1. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA. nusratmatin@gmail.com. 2. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA. 3. Department of Pharmacology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, NV, USA.
Abstract
OBJECTIVE: Chronic hypertension induces detrimental changes in the structure and function of surface cerebral arteries. Very little is known about PAs, which perfuse distinct neuronal populations in the cortex and may play a role in cerebrovascular disorders. We investigated the effect of DOCA-salt induced hypertension on endothelial function and artery structure in PAs and MCAs. METHODS: Uninephrectomized male Sprague-Dawley rats were implanted with a subcutaneous pellet containing DOCA (150 mg/kg b.w.) and drank salt water (1% NaCl and 0.2% KCl) for 4 weeks. Sham rats were uninephrectomized and drank tap water. Vasoreactivity and passive structure in the MCAs and the PAs were assessed by pressure myography. RESULTS: Both MCAs and PAs from DOCA-salt rats exhibited impaired endothelium-dependent dilation (P<.05). In the PAs, addition of NO and COX inhibitors enhanced dilation in DOCA-salt rats (P<.05), suggesting that dysfunctional NO and COX-dependent signaling could contribute to impaired endothelium-mediated dilation. MCAs from DOCA-salt rats exhibited inward remodeling (P<.05). CONCLUSIONS: Hypertension-induced MCA remodeling coupled with impaired endothelium-dependent dilation in both the MCAs and PAs may exacerbate the risk of cerebrovascular accidents and the associated morbidity and mortality.
OBJECTIVE: Chronic hypertension induces detrimental changes in the structure and function of surface cerebral arteries. Very little is known about PAs, which perfuse distinct neuronal populations in the cortex and may play a role in cerebrovascular disorders. We investigated the effect of DOCA-salt induced hypertension on endothelial function and artery structure in PAs and MCAs. METHODS: Uninephrectomized male Sprague-Dawley rats were implanted with a subcutaneous pellet containing DOCA (150 mg/kg b.w.) and drank saltwater (1% NaCl and 0.2% KCl) for 4 weeks. Sham rats were uninephrectomized and drank tapwater. Vasoreactivity and passive structure in the MCAs and the PAs were assessed by pressure myography. RESULTS: Both MCAs and PAs from DOCA-saltrats exhibited impaired endothelium-dependent dilation (P<.05). In the PAs, addition of NO and COX inhibitors enhanced dilation in DOCA-saltrats (P<.05), suggesting that dysfunctional NO and COX-dependent signaling could contribute to impaired endothelium-mediated dilation. MCAs from DOCA-saltrats exhibited inward remodeling (P<.05). CONCLUSIONS:Hypertension-induced MCA remodeling coupled with impaired endothelium-dependent dilation in both the MCAs and PAs may exacerbate the risk of cerebrovascular accidents and the associated morbidity and mortality.
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