Circadian Clock in Angiotensin II Induced Hypertension and Vascular Disease

Hdl Handle:
http://hdl.handle.net/10675.2/621664
Title:
Circadian Clock in Angiotensin II Induced Hypertension and Vascular Disease
Authors:
Pati, Paramita
Abstract:
Hypertension remains a major risk factor for cardiovascular disease and death. While clinical studies and guideline recommendations underscore the benefits of reducing sodium intake in the treatment of high blood pressure, recent human data suggest that underlying conditions of disease may confound these positive effects of low salt diets. Herein, we examined the influence of circadian dysfunction during experimental hypertension caused by angiotensin II (Ang II), a key peptide in blood pressure regulation. While a low salt diet caused the expected decrease in blood pressure in wild type (WT) mice, mice with disruption of the circadian clock exhibited a paradoxical response to low salt. Mice with disruption in the circadian clock component Period (Period-knockout/KO mice), were abolished in blood pressure rhythm due to an increase in daytime blood pressure. This impairment in blood pressure rhythm in Per-KO mice on the low salt diet was restored to rhythmic oscillation by the angiotensin receptor blocker losartan. Similarly, exogenous administration of Ang Il caused a non-dipping blood pressure phenotype in the Per-KO mice on a normal salt diet, which resulted in pathological thickening of the vasculature indicative of vascular disease. These effects were related to circadian rhythm as impairment in blood pressure caused by low salt was recapitulated in WT mice induced to circadian derangement by a shortened light cycle. Further thickening of the vasculature and increased renin levels were observed in Per-KO mice on a chronic low salt diet but not in WT mice. Moreover, disruption of the Period gene altered ATI receptor expression and other components of the renin-angiotensin system. These data suggest that circadian dysfunction may compromise the benefits of a low salt diet and support recent clinical data that raise caution to sodium restriction as a therapy for hypertension.
Affiliation:
Department of Pharmacology and Toxicology
Issue Date:
2015
URI:
http://hdl.handle.net/10675.2/621664
Additional Links:
http://ezproxy.augusta.edu/login?url=https://search.proquest.com/docview/1662484155?accountid=12365
Type:
Dissertation
Appears in Collections:
Department of Pharmacology and Toxicology Theses and Dissertations; Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorPati, Paramitaen
dc.date.accessioned2017-12-29T16:32:57Z-
dc.date.available2017-12-29T16:32:57Z-
dc.date.issued2015-
dc.identifier.urihttp://hdl.handle.net/10675.2/621664-
dc.description.abstractHypertension remains a major risk factor for cardiovascular disease and death. While clinical studies and guideline recommendations underscore the benefits of reducing sodium intake in the treatment of high blood pressure, recent human data suggest that underlying conditions of disease may confound these positive effects of low salt diets. Herein, we examined the influence of circadian dysfunction during experimental hypertension caused by angiotensin II (Ang II), a key peptide in blood pressure regulation. While a low salt diet caused the expected decrease in blood pressure in wild type (WT) mice, mice with disruption of the circadian clock exhibited a paradoxical response to low salt. Mice with disruption in the circadian clock component Period (Period-knockout/KO mice), were abolished in blood pressure rhythm due to an increase in daytime blood pressure. This impairment in blood pressure rhythm in Per-KO mice on the low salt diet was restored to rhythmic oscillation by the angiotensin receptor blocker losartan. Similarly, exogenous administration of Ang Il caused a non-dipping blood pressure phenotype in the Per-KO mice on a normal salt diet, which resulted in pathological thickening of the vasculature indicative of vascular disease. These effects were related to circadian rhythm as impairment in blood pressure caused by low salt was recapitulated in WT mice induced to circadian derangement by a shortened light cycle. Further thickening of the vasculature and increased renin levels were observed in Per-KO mice on a chronic low salt diet but not in WT mice. Moreover, disruption of the Period gene altered ATI receptor expression and other components of the renin-angiotensin system. These data suggest that circadian dysfunction may compromise the benefits of a low salt diet and support recent clinical data that raise caution to sodium restriction as a therapy for hypertension.en
dc.relation.urlhttp://ezproxy.augusta.edu/login?url=https://search.proquest.com/docview/1662484155?accountid=12365en
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
dc.subjectBiological sciencesen
dc.subjectHealth and environmental sciencesen
dc.subjectAngiotensin IIen
dc.subjectCircadian clocken
dc.subjectCircadian dysfunctionen
dc.subjectHypertensionen
dc.subjectLow Salten
dc.subjectVascular Diseaseen
dc.titleCircadian Clock in Angiotensin II Induced Hypertension and Vascular Diseaseen
dc.typeDissertationen
dc.contributor.departmentDepartment of Pharmacology and Toxicologyen
dc.description.advisorRudic, Danen
dc.description.committeen/aen
dc.description.degreePh.D.en
dc.description.majorDoctor of Philosophy with a Major in Pharmacologyen
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