Author ORCID Identifier

https://orcid.org/0000-0001-7494-9815

Year of Publication

2018

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Arts and Sciences

Department

Biology

First Advisor

Dr. Jeffrey L. Osborn

Abstract

Hypertension is a complex multifactorial pathology that is a major risk factor for the development of cardiovascular disease, stroke, and end stage renal disease. In the United States, hypertension affects over 1 in 3 adults and comprises an annual cost of over $58 billion in the healthcare industry. While remarkable strides in the diagnosis and treatment of hypertension have been made since the pathology was first treated in the 1960s, a remarkable 13% of patients with elevated blood pressures are classified as resistant hypertensive, where blood pressure remains uncontrolled while on three or more classes of anti-hypertensive drugs. This treatment gap suggests that researchers need to develop and utilize translational models that recapitulate the pathologies seen in patient populations. Non-human primates (NHP) are highly similar to humans in terms of physiology, circadian rhythmicity, behavior, and gene sequence and structure. Development of NHP models that spontaneously develop pathologies, like spontaneous hypertension, provide novel and vital tools to studying disease. Overall, this dissertation is a comparative analysis of the mechanisms that drive the development of spontaneous hypertension in Chlorocebus aethiops sabaeus, an Old World non-human primate, and known mediators of essential hypertension in human populations. Chapter 2 presents how hypertensive (HT) African Green Monkeys (AGMs) are older, with elevated heart rates, increased renal vascular wall/lumen ratios, and altered glomerular morphologies compared to normotensive (NT) controls. Chapter 3 describes metabolic studies performed in a large cohort of animals that identified elevated proteinuria and ion excretion in HT AGMs compared to NT animals. Chapter 4 focuses on the contribution of sympathetic nervous system to the development of hypertension in this animal model and describes the significant left ventricular hypertrophy and elevation of adrenergic receptor mRNA in HT AGMs. Chapter 5 examines how age affects hypertension and renal function in the NT and HT AGMs. Together these data provide a foundational basis for the development of spontaneous hypertension in the AGM and provide a novel translational model for the study of cardiovascular disease.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2018.374

Funding Information

This work funded in part by an American Heart Association pre-doctoral grant awarded to M. K. Rhoads (16PRE30010011).

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Physiology Commons

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