All ETDs from UAB

Advisory Committee Chair

David M Pollock

Advisory Committee Members

Karen Gamble

Shannon Bailey

Edward Inscho

Darwin Bell

Jennifer Pollock

Document Type

Dissertation

Date of Award

2020

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Many physiological processes, including blood pressure (BP) regulation, follow specific rhythms tied to a 24-h cycle. This is largely because circadian genes operate in virtually every cell type in the body. In healthy individuals, BP during nighttime is 10-20% lower compared to daytime, a phenomenon known as “nocturnal dipping”. It is acknowledged that the dipping of BP is essential in maintaining normal cardiovascular and renal function. However, it remains unclear as to what factors contribute to nocturnal dipping. The purpose of this dissertation is to elucidate mechanisms underlying the circadian rhythm of BP. Bmal1 is one of the core circadian clock genes and has been shown to regulate BP and electrolyte homeostasis. A major finding of this study is that Bmal1 in the collecting duct does not affect the circadian rhythm of BP, but rather regulates the number of BP in male mice. Female mice, however, do not exhibit any alteration in BP in the absence of collecting duct Bmal1. In addition, renal excretions of electrolytes, endothelin-1 and aldosterone are not affected by collecting duct Bmal1. The second part of the dissertation determines the relationships between timing of food intake and circadian rhythm of BP. BP was measured in healthy mice that were fed only during their inactive period. There was an inverted circadian rhythm of BP; however, renal excretion of electrolytes remained largely unaffected. Overall, this dissertation provides evidence that Bmal1 in the renal collecting duct is not required to maintain BP rhythm. In addition, timing of food intake is important in regulating BP rhythm in mice.

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