Blood pressure impacts the renal T cell profile of male and female spontaneously hypertensive rats

Hdl Handle:
http://hdl.handle.net/10675.2/325835
Title:
Blood pressure impacts the renal T cell profile of male and female spontaneously hypertensive rats
Authors:
Tipton, Ashlee J.
Abstract:
Of the 68 million Americans with hypertension, fewer than 46% have their blood pressure (BP) adequately controlled and women are more likely than men to have uncontrolled hypertension. This underscores the critical need for new treatment options; however, this is a challenge due to our lack of knowledge regarding the mechanism(s) driving essential hypertension. T cells have been implicated in hypertension in males. Prior to our work, the role of T cells in hypertensive females had been unexplored. We demonstrate that female spontaneously hypertensive rats (SHR) have a decrease in BP in response to an immunosuppressant, supporting an immune component to their hypertension. We further defined a sex difference in the renal T cell and cytokine profile in SHR. Female SHR have a more anti-inflammatory immune profile in their kidneys than males. To gain insight into the mechanisms mediating sex differences in the immune profile, male and female SHR were gonadectomized. Gonadectomy increased pro-inflammatory markers in both sexes and attenuated anti-inflammatory markers particularly in females. Therefore, while both male and female sex hormones promote an anti-inflammatory immune profile, female ii sex hormones contribute greater to their more anti-inflammatory profile, but do not explain the sex difference. To determine the impact of hypertension on the renal immune profile, experiments measured renal T cells and cytokines in hypertensive male and female SHR, normotensive Wistar Kyoto rats (WKY), and SHR treated with antihypertensive therapy. All T cells and cytokines measured were higher in SHR compared to the same sex WKY. Moreover, antihypertensive therapy decreased renal Tregs only in female SHR. These data suggest that increased BP in both sexes is associated with an increase in renal inflammation; however female SHR have a compensatory increase in renal Tregs in response to increases in BP. TGF-β is a key cytokine regulating Treg and Th17 differentiation and we found that female SHR express more TGF-β than males. Experiments assessed if female SHR possessed a sex hormone or BP-mediated increase in renal TGF- β corresponding with increases in Tregs. We determined that loss of female sex hormones and increased BP in female SHR increase renal TGF-β expression. We conclude that BP status drive sex differences in the renal T cell and cytokine profile of SHR.
Affiliation:
Department of Physiology
Issue Date:
Mar-2014
URI:
http://hdl.handle.net/10675.2/325835
Additional Links:
http://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/1517984809?accountid=12365
Type:
Dissertation
Language:
en
Appears in Collections:
Theses and Dissertations; Department of Physiology Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorTipton, Ashlee J.en
dc.date.accessioned2014-09-03T20:25:33Z-
dc.date.available2014-09-03T20:25:33Z-
dc.date.issued2014-03-
dc.identifier.urihttp://hdl.handle.net/10675.2/325835-
dc.description.abstractOf the 68 million Americans with hypertension, fewer than 46% have their blood pressure (BP) adequately controlled and women are more likely than men to have uncontrolled hypertension. This underscores the critical need for new treatment options; however, this is a challenge due to our lack of knowledge regarding the mechanism(s) driving essential hypertension. T cells have been implicated in hypertension in males. Prior to our work, the role of T cells in hypertensive females had been unexplored. We demonstrate that female spontaneously hypertensive rats (SHR) have a decrease in BP in response to an immunosuppressant, supporting an immune component to their hypertension. We further defined a sex difference in the renal T cell and cytokine profile in SHR. Female SHR have a more anti-inflammatory immune profile in their kidneys than males. To gain insight into the mechanisms mediating sex differences in the immune profile, male and female SHR were gonadectomized. Gonadectomy increased pro-inflammatory markers in both sexes and attenuated anti-inflammatory markers particularly in females. Therefore, while both male and female sex hormones promote an anti-inflammatory immune profile, female ii sex hormones contribute greater to their more anti-inflammatory profile, but do not explain the sex difference. To determine the impact of hypertension on the renal immune profile, experiments measured renal T cells and cytokines in hypertensive male and female SHR, normotensive Wistar Kyoto rats (WKY), and SHR treated with antihypertensive therapy. All T cells and cytokines measured were higher in SHR compared to the same sex WKY. Moreover, antihypertensive therapy decreased renal Tregs only in female SHR. These data suggest that increased BP in both sexes is associated with an increase in renal inflammation; however female SHR have a compensatory increase in renal Tregs in response to increases in BP. TGF-β is a key cytokine regulating Treg and Th17 differentiation and we found that female SHR express more TGF-β than males. Experiments assessed if female SHR possessed a sex hormone or BP-mediated increase in renal TGF- β corresponding with increases in Tregs. We determined that loss of female sex hormones and increased BP in female SHR increase renal TGF-β expression. We conclude that BP status drive sex differences in the renal T cell and cytokine profile of SHR.en
dc.language.isoenen
dc.relation.urlhttp://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/1517984809?accountid=12365en
dc.subjectKidneyen
dc.subjectSHRen
dc.subjectessential hypertensionen
dc.subjectSexen
dc.subjectT cellen
dc.subjectTGF-betaen
dc.titleBlood pressure impacts the renal T cell profile of male and female spontaneously hypertensive ratsen
dc.typeDissertationen
dc.contributor.departmentDepartment of Physiology-
dc.description.advisorSullivan, Jennifer C.en
dc.description.committeePollock, Jennifer; Pollock, David; Webb, Clinton; Baban, Babak; Ergul, Adviye-
dc.description.degreeDoctor of Philosophy (Ph.D.)-
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