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dc.contributor.authorSpradley, Frank T.
dc.date.accessioned2014-06-06T16:31:34Z
dc.date.available2014-06-06T16:31:34Z
dc.date.issued2011en
dc.identifier.urihttp://hdl.handle.net/10675.2/319915
dc.description.abstractDahl salt-sensitive (SS) rats are genetically predisposed to cardiovascular-renal disease. These studies examined cardiovascular-renal outcomes in response to a high-fat diet/normal-salt diet in SS rats. In a separate study, we examined cardiovascular-renal disease risk in SS rats on different standard chow diet/normal-salt diets. We tested the hypotheses that: (1) a high-fat diet induces hypertension and renal injury in SS rats; (2) a high-fat diet enhances aortic vasoconstriction in SS rats; (3) a high-fat diet induces aortic perivascular adipose tissue (PVAT) dysfunction in SS rats; and (4) two standard chow diets, namely AIN-76A and Teklad diet, induce differential vasoconstriction or vasorelaxation phenotypes in aorta and small mesenteric arteries from SS rats. In the high-fat diet studies, rats were provided high-fat diet starting at 12 weeks old. At 16 weeks old, SS rats on the high-fat diet had hypertension and greater renal glomerular and tubular injury than SS-13BN rats. SS rats supplemented with the immunosuppressive drug mycophenolate mofetil (MMF; 30 mg/kg/day, oral) for the duration of the high-fat diet did not develop hypertension. High-fat diet was associated with reduced vasoconstrictive response to angiotensin II and increased acetylcholine-mediated vasorelaxation in SS rats via increased nitric oxide synthase (NOS) function in comparison to SS rats maintained on a normal-fat/normal-salt diet. In regards to PVAT function, high-fat diet increased thoracic aorta PVAT deposition and induced PVAT-mediated blunting of aortic vasoconstriction. In the standard chow diet studies, 16-week old SS rats placed on the AIN or Teklad diet at weaning had similar NOS functional regulation of vasoconstriction and vasorelaxation in large and small arteries. However, by using a diet-switch protocol, we demonstrated that SS rats placed on AIN diet at weaning and changed to Teklad diet at 12 weeks old had reduced NOS-mediated vasorelaxation and reduced NOS buffering of vasoconstriction in small arteries from SS rats, which was not observed in the corresponding diet-switch group. In conclusion, these studies highlight differential renal and vascular responses to a short-term high-fat diet, and even changes in standard chow diet, when genetically predisposed to hypertension.
dc.language.isoenen
dc.relation.urlhttp://search.proquest.com/docview/1018407647?accountid=12365en
dc.subjectAortaen
dc.subjectDahl salt-sensitive raten
dc.subjecthigh-fat dieten
dc.subjectkidneyen
dc.subjectmesentric arteriesen
dc.subjectnitric oxide synthaseen
dc.subjectperivascular adipose tissueen
dc.subjectSS-13BN raten
dc.subjectstandard chow dieten
dc.subjectvascular reactivityen
dc.titleMechanisms of Diet-Induced Hypertension and Vascular Disease Risk in Dahl Ratsen
dc.typeDissertationen
dc.contributor.departmentDepartment of Medicineen
dc.description.advisorPollock, Jennifer S.en
dc.description.degreeDoctor of Philosophy (Ph.D.)en
dc.description.committeeCatravas, John; Harshfield, Gregory; Pollock, David; Sullivan, Jenniferen
html.description.abstractDahl salt-sensitive (SS) rats are genetically predisposed to cardiovascular-renal disease. These studies examined cardiovascular-renal outcomes in response to a high-fat diet/normal-salt diet in SS rats. In a separate study, we examined cardiovascular-renal disease risk in SS rats on different standard chow diet/normal-salt diets. We tested the hypotheses that: (1) a high-fat diet induces hypertension and renal injury in SS rats; (2) a high-fat diet enhances aortic vasoconstriction in SS rats; (3) a high-fat diet induces aortic perivascular adipose tissue (PVAT) dysfunction in SS rats; and (4) two standard chow diets, namely AIN-76A and Teklad diet, induce differential vasoconstriction or vasorelaxation phenotypes in aorta and small mesenteric arteries from SS rats. In the high-fat diet studies, rats were provided high-fat diet starting at 12 weeks old. At 16 weeks old, SS rats on the high-fat diet had hypertension and greater renal glomerular and tubular injury than SS-13BN rats. SS rats supplemented with the immunosuppressive drug mycophenolate mofetil (MMF; 30 mg/kg/day, oral) for the duration of the high-fat diet did not develop hypertension. High-fat diet was associated with reduced vasoconstrictive response to angiotensin II and increased acetylcholine-mediated vasorelaxation in SS rats via increased nitric oxide synthase (NOS) function in comparison to SS rats maintained on a normal-fat/normal-salt diet. In regards to PVAT function, high-fat diet increased thoracic aorta PVAT deposition and induced PVAT-mediated blunting of aortic vasoconstriction. In the standard chow diet studies, 16-week old SS rats placed on the AIN or Teklad diet at weaning had similar NOS functional regulation of vasoconstriction and vasorelaxation in large and small arteries. However, by using a diet-switch protocol, we demonstrated that SS rats placed on AIN diet at weaning and changed to Teklad diet at 12 weeks old had reduced NOS-mediated vasorelaxation and reduced NOS buffering of vasoconstriction in small arteries from SS rats, which was not observed in the corresponding diet-switch group. In conclusion, these studies highlight differential renal and vascular responses to a short-term high-fat diet, and even changes in standard chow diet, when genetically predisposed to hypertension.


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