A role for beta-receptors in modulating carotid body sensitivity following chronic intermittent hypoxia exposure at adulthood and prenatally

Alzahrani, Abdulaziz Abdullah ORCID: 0000-0001-5973-2802 (2022). A role for beta-receptors in modulating carotid body sensitivity following chronic intermittent hypoxia exposure at adulthood and prenatally. University of Birmingham. Ph.D.

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Abstract

The carotid body (CB) is a peripheral chemoreceptor located near the bifurcation of the common carotid artery responsible for detecting and responding to changes in arterial oxygen, carbon dioxide, and pH. Several studies have indicated that chronic over-activation of the CB in diseases such as obstructive sleep apnoea (OSA) play a vital role in promoting neural hypertension, heart failure, and other co-morbidities. The role of adrenaline in stimulating the CB has been recently implicated, and a chronic increase of the plasma concentration of adrenaline is evident in OSA patients and animals exposed to chronic intermittent hypoxia (CIH). However, the role of chronic adrenergic activation in driving CB hyperactivity has yet to be understood. The incidence of OSA increases during pregnancy and may give rise to exposure of the fetus to CIH. Exposure of the fetus to suboptimal conditions in utero can lead to IUGR and altered fetal developmental trajectory result in inducing developmental programming that may develop into chronic diseases later in life. The potential impact of CIH exposure in utero that might lead to induce developmental programming of the fetal CB lasting into adulthood has not been previously investigated. There are two primary aims of this research project: 1. To investigate whether chronic administration of beta-blocker (propranolol) was able to prevent driving CB hyperactivity in CIH animal model, 2. To examine whether CIH exposure during pregnancy promotes changes in the CB function in adult offspring. The result showed that \(\beta\)-adrenoceptors is expressed in the CB type I cell. Targeting these receptors with \(\beta\)-adrenoceptor blockade prevented the CIH-induced CB hyperactivity. It has also been shown that prenatal CIH altered CB function and sensitivity responses to different stimuli in the adult offspring.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):