Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure Control.

Daniela Patinha,Wioletta Pijacka,Julian F R Paton,Maarten P Koeners

doi:10.3389/fphys.2017.00752

Daniela Patinha, Wioletta Pijacka + Show 2 more

Open Access

https://doi.org/10.3389/fphys.2017.00752

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Abstract

Oxygen sensing mechanisms are vital for homeostasis and survival. When oxygen levels are too low (hypoxia), blood flow has to be increased, metabolism reduced, or a combination of both, to counteract tissue damage. These adjustments are regulated by local, humoral, or neural reflex mechanisms. The kidney and the carotid body are both directly sensitive to falls in the partial pressure of oxygen and trigger reflex adjustments and thus act as oxygen sensors. We hypothesize a cooperative oxygen sensing function by both the kidney and carotid body to ensure maintenance of whole body blood flow and tissue oxygen homeostasis. Under pathological conditions of severe or prolonged tissue hypoxia, these sensors may become continuously excessively activated and increase perfusion pressure chronically. Consequently, persistence of their activity could become a driver for the development of hypertension and cardiovascular disease. Hypoxia-mediated renal and carotid body afferent signaling triggers unrestrained activation of the renin angiotensin-aldosterone system (RAAS). Renal and carotid body mediated responses in arterial pressure appear to be synergistic as interruption of either afferent source has a summative effect of reducing blood pressure in renovascular hypertension. We discuss that this cooperative oxygen sensing system can activate/sensitize their own afferent transduction mechanisms via interactions between the RAAS, hypoxia inducible factor and erythropoiesis pathways. This joint mechanism supports our view point that the development of cardiovascular disease involves afferent nerve activation.

Highlights

Oxygen is essential for aerobic metabolism, a fundamental mechanism for energy production
Hypoxichypoperfusion of the kidney and carotid body is a likely trigger for increased reflex sympathetic activity (Koeners et al, 2016) and aberrant afferent drive from these organs is implicated in the etiology of neurogenic hypertension (Fisher and Paton, 2012; Narkiewicz et al, 2016; Silva et al, 2016; Osborn and Foss, 2017)
Carotid body chemoreceptor signaling to the adrenal medulla selectively upregulates HIF1α expression, inducing catecholamine secretion and blood pressure rise (Peng et al, 2014; Kumar et al, 2015), the latter is eliminated by adrenal demedullation (Bao et al, 1997)

Summary

INTRODUCTION

Oxygen is essential for aerobic metabolism, a fundamental mechanism for energy production. The delivery of optimal levels of oxygen to tissues must be highly regulated as both insufficient (hypoxia) or excessive oxygen levels (hyperoxia) are highly detrimental. Tissue oxygenation has been found to be reduced during pathological conditions such as cancer (Liu et al, 2016), diabetes (Palm et al, 2003), hypertension (Welch et al, 2001), chronic kidney disease (Milani et al, 2016), and stroke (Ferdinand and Roffe, 2016). We will explore the idea that an inappropriate activation of some of the signaling pathways that counteract hypoxia can contribute to the development of hypertension and cardiovascular disease through activation of the sympathetic nervous system

Hypoxia in Hypertension

Renal Oxygenation

Carotid Body Oxygenation

CLINICAL PERSPECTIVE