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dc.contributor.authorRigsby, Christine Spring
dc.date.accessioned2021-03-31T19:09:21Z
dc.date.available2021-03-31T19:09:21Z
dc.date.issued2006-12
dc.identifier.urien
dc.identifier.urihttp://hdl.handle.net/10675.2/623946
dc.description.abstractStroke is the third leading cause of death ·and the leading cause of long-term disability in the United States, where approximately 88% of stroke occurrences are ischemic in origin. Hypertension is a primary risk factor for stroke. Elevated aldosterone levels have also been identified as a risk factor for stroke, as patients with primary aldosteronism incur increased incidences of cardiovascularrelated pathologies than do patients with essential hypertension. Previous studies from our laboratory have shown that mineralocorticoid (aldosterone) receptor (MR) activation can induce deleterious vascular remodeling and, conversely, blockade of the MR with spironolactone reduces cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP). It is known from studies in SHRSP that cerebral vessel structure is directly related to infarct size. We hypothesized that chronic spironolactone treatment would alter cerebral vessel structure. Six-week-old male SHRSP were treated with spironolactone for six weeks and passive vessel structure was analyzed using a pressurized arteriograph. Spironolactone treatment prevented cerebral vessel remodeling. From a clinical standpoint, many patients present with pre-existing vascular damage; therefore, we hypothesized that chronic MR antagonism would reverse existing vascular damage. Twelve-week-old male SHRSP were treated as described above. Interestingly, spironolactone treatment partially reversed existing cerebral vessel remodeling. Recent analysis of data from the Framingham Heart Study show that females may be more sensitive to the effects of aldosterone, but few studies looking at MR blockade have been performed in females. Similar ischemic stroke and vascular analysis studies were performed in 12-week-old female SHRSP. Contrary to the male studies, MR antagonism, using spironolactone or eplerenone, did not reduce damage from ischemic stroke or improve vessel structure. MR protein expression was evaluated in cerebral arteries collected from 12-week-old male and female SHRSP using Western blot analysis. Surprisingly, female SHRSP had increased MR expression, compared to male SHRSP. These novel studies uncover an apparent sexual dimorphism in the actions of MR antagonists and expression ofthe.MR in SHRSP. The action of the MR antagonists may be influenced by differential MR expression and this could help to explain the sex difference observed. existing cerebral vessel remodeling. Recent analysis of data from the Framingham Heart Study show that females may be more sensitive to the effects of aldosterone, but few studies looking at MR blockade have been performed in females. Similar ischemic stroke and vascular analysis studies were performed in 12-week-old female SHRSP. Contrary to the male studies, MR antagonism, using spironolactone or eplerenone, did not reduce damage from ischemic stroke or improve vessel structure. MR protein expression was evaluated in cerebral arteries collected from 12-week-old male and female SHRSP using Western blot analysis. Surprisingly, female SHRSP had increased MR expression, compared to male SHRSP. These novel studies uncover an apparent sexual dimorphism in the actions of MR antagonists and expression ofthe.MR in SHRSP. The action of the MR antagonists may be influenced by differential MR expression and this could help to explain the sex difference observed. existing cerebral vessel remodeling. Recent analysis of data from the Framingham Heart Study show that females may be more sensitive to the effects of aldosterone, but few studies looking at MR blockade have been performed in females. Similar ischemic stroke and vascular analysis studies were performed in 12-week-old female SHRSP. Contrary to the male studies, MR antagonism, using spironolactone or eplerenone, did not reduce damage from ischemic stroke or improve vessel structure. MR protein expression was evaluated in cerebral arteries collected from 12-week-old male and female SHRSP using Western blot analysis. Surprisingly, female SHRSP had increased MR expression, compared to male SHRSP. These novel studies uncover an apparent sexual dimorphism in the actions of MR antagonists and expression ofthe.MR in SHRSP. The action of the MR antagonists may be influenced by differential MR expression and this could help to explain the sex difference observed.en_US
dc.language.isoen_USen_US
dc.publisherAugusta Universityen_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.subjectischemic strokeen_US
dc.subjecthypertensionen_US
dc.subjectvascular remodelingen_US
dc.subjectmiddle cerebral arteryen_US
dc.titleThe effect of mineralocorticoid receptor antagonism on ischemic infarct size and cerebral vessel structure in male and femail spontaneously hypertensive stroke-prone rats: sex difference revealed.en_US
dc.typeDissertationen_US
dc.contributor.departmentMedical College of Georgiaen_US
dc.description.advisorDorrance, Anne
dc.description.committeeErgul
dc.description.committeeInscho
dc.description.committeeMcCluskey
dc.description.committeeWebb
dc.description.degreeDoctor of Philosophyen_US
dc.embargoen
refterms.dateFOA2021-03-31T19:09:22Z


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