Grant: $66,390 - National Institutes of Health - Sep. 18, 2009
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Award Description: The long-term goal of our program is to better understand the regulation of cerebrovascular function and structure, in order to identify new targets and develop new strategies for prevention and treatment of stroke in diabetes. The central hypothesis of the parent grant was that diabetes-induced changes in the endothelin (ET) system promote hypertrophic remodeling of cerebral microvessels via MMP-mediated activation of cell surface-bound growth signals. Studies completed to date provided evidence that even short term, moderate diabetes promotes significant remodeling of the blood vessels and this response can be prevented by ET receptor blockade. We also showed that there is an upregulation of contractile ETB receptors on vascular smooth muscle. Since the regulation of vascular tonus is critical for cerebral blood flow, a key question that remains to be answered is to what extent diabetes-mediated remodeling and changes in ET receptor profile affect vascular function. This is important to better understand the role of diabetes-mediated cerebrovascular remodeling on cerebrovascular complications of diabetes and fully evaluate whether ET receptor antagonism may be a potential therapeutic target in the prevention of cerebrovascular disease and stroke associate with diabetes. We have evidence that ischemic brain injury causes smaller infarction in diabetic rats that display enhanced remodeling suggesting potential neuroprotection in early diabetes. Accordingly, the hypothesis of this supplemental application is that diabetes mediates compensatory hypertrophic remodeling to maintain vascular tonus to prevent the downstream microvessels. To test this hypothesis, we will measure myogenic and endocrine reactivity of middle cerebral arteries (MCAs) from vehicle and dual ET receptor antagonist-treated control and diabetic Goto-Kakizaki rats under normal and ischemic conditions. Completion of these studies will significantly enhance our understanding of the pathophysiological basis of cerebrovascular complications associated with diabetes and development of cerebrovascular protection strategies to retard the progression, delay the onset and even possibly prevent cerebrovascular disease and stroke in diabetes.
Project Description: As defined in the award description field
Jobs Summary: Personnel processing started. (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 18, 2009. Help expand these official descriptions using the wiki below.