Experimental Physiology
92.1 pp 19-20
DOI: 10.1113/expphysiol.2006.036616
© The Physiological Society 2007
Sleep Apnoea and Hypertension: Physiological Bases for a Causal Relation Themed Issue
Michael L. Smith1
1 University of North Texas Health Science Center, Integrative Physiology, 3500 Camp Bowie Bloulevard, Fort Worth, TX 76107, USA
 |
Introduction
|
|---|
Sleep apnoea, once thought of as a disease of morbid obesity, is now recognized as a prevalent disease that is a significant risk factor for many serious comorbid conditions with cardiovascular disease. This field of investigation has evolved from the clinical observation of a strong association between sleep apnoea and hypertension, to epidemiological data reported in the 1980s. From these clinical observations several lines of investigation have emerged to test whether there is a causal relationship. The resulting literature has consistently shown that intermittent apnoea, in particular intermittent hypoxia, is the primary culprit in the physiological changes accompanying sleep apnoea which provoke the increased risk of hypertension. How this unique stimulus leads to physiological adaptations that can culminate in hypertension has been the focus of intense investigation over the past 15 years. In the spirit of Experimental Physiology's commitment to address integrative and translational physiology, this themed issue provides a series of review articles which bridge cellular and molecular mechanisms of physiological adaptations to intermittent apnoea to the strong clinical association between sleep apnoea and hypertension.
The primary physiological mechanism linking sleep apnoea and hypertension is the well-established chronic elevation of sympathetic nerve activity (whether measured by circulating catecholamines or by microneurography) that is present during sleep and wakefulness. This often rivals the activity seen in patients with congestive heart failure. Acutely, apnoea leads to increased sympathetic nerve activity by activating the arterial chemoreceptors and by withdrawing the respiratory modulation of sympathetic discharge. This has led to the hypothesis that the chemoreflex is, in part, responsible for the chronic elevation of sympathetic activity. Consequently, a major focus of this themed issue is on the manner in which the chemoreflex adapts to intermittent hypoxia or apnoea. A hallmark of essential hypertension is vascular dysfunction, and there is now a growing body of evidence suggesting that intermittent hypoxia can lead to vascular dysfunction, which is the focus of the review by Foster et al. (2007). Last, since hypertension is a core disease process integral to the metabolic syndrome, the final review addresses the possible links between sleep apnoea and the metabolic syndrome (Wolk & Somers, 2007).
|
The review articles
|
|---|
The clinical link between sleep apnoea and hypertension involves partly the comorbid states associated with sleep apnoea; however, evidence is growing to support a causative role of sleep apnoea. The evidence for this and some of the potential mechanisms, including the role of altered chemoreflex function in patients and the potential link to specific neuromodulators such as angiotensin II and endothelin, is reviewed by Weiss et al. (2007). Brainstem processing of chemoreceptor afferent input is the primary target for both short-term and long-term adaptations of respiratory control. Long-term facilitation of respiratory control is a model of central adaptation which appears to play a role in the occurrence and/or protection against apnoea as reviewed by Mahamad & Mitchell (2007). Since sympathetic efferent activity is chronically elevated with non-sustained intermittent hypoxia, it is likely that altered brainstem processing may be a contributing factor. How the adaptive mechanisms for respiratory control and sympathetic neural control are related is an important target for future mechanistic investigations. The evidence that chemoreflex function is affected by intermittent hypoxia or apnoea is consistent in both animals and humans. Prabhakar et al. (2007) review the specific adaptations which occur at the carotid body receptors and demonstrate that there is altered afferent neural regulation from the chemoreceptors and altered processing within the central nervous system. These investigators also provide compelling evidence for an important role of reactive oxygen species and hypoxia-inducible factor-1 in the cellular and molecular signalling mechanisms linking intermittent hypoxia to sustained sympathoexcitation. Considerable data from humans also confirm that chemoreflex control of sympathetic activity is altered with intermittent hypoxia or apnoea. The potential mechanisms that have been explored include altered gain, resetting and sustained chemoreceptor activation. These potential mechanisms and how they may contribute to the chronic elevation of sympathetic activity are reviewed (Smith & Pacchia, 2007; Weiss et al. 2007). For these changes in neural control to translate into essential hypertension, sustained alterations of cardiac, renal and/or vascular function must occur. Consistent with most forms of hypertension, evidence is accumulating to suggest that endothelial dysfunction and impaired vascular control are a consequence of intermittent hypoxia and thus are likely to comprise a causative outcome linking sleep apnoea to hypertension. Foster et al. (2007) review the evidence supporting this premise. Finally, the relationship of sleep apnoea to hypertension combined with its association with obesity and diabetes implies that sleep apnoea is likely to grossly increase the risk of the metabolic syndrome. In fact, sleep apnoea should perhaps be considered a component of the metabolic syndrome. The final review by Wolk & Somers (2007) explores the strong evidence linking sleep apnoea to obesity, insulin resistance, diabetes, lipid dysfunction, inflammatory disorders and hypertension, and thereby provides a compelling argument for its role in the metabolic syndrome.
In conclusion, this themed issue provides a foundation of the primary mechanisms that appear to link sleep apnoea to hypertension and to the metabolic syndrome. As future research extends these findings, this foundation of knowledge will provide not only the catalyst for better understanding of these causative relationships, but also the potential for new strategies for treating hypertension and the other disease processes of the metabolic syndrome.
|
References
|
|---|
Foster GE, Poulin MJ & Hanly PJ (2007). Intermittent hypoxia and vascular function: implications for obstructive sleep apnoea. Exp Physiol 92, 51–65.[Abstract/Free Full Text]Mahamed S & Mitchell GS (2007). Is there a link between intermittent hypoxia-induced respiratory plasticity and obstructive sleep apnoea? Exp Physiol 92, 27–37.[Abstract/Free Full Text]
Prabhakar NR, Dick TE, Nanduri J & Kumar GK (2007). Systemic, cellular and molecular analysis of chemoreflex-mediated sympathoexcitation by chronic intermittent hypoxia. Exp Physiol 92, 39–44.[Abstract/Free Full Text]
Smith ML & Pacchia CF (2007). Sleep apnoea and hypertension: role of chemoreflexes in humans. Exp Physiol 92, 45–50.[Abstract/Free Full Text]
Weiss JW, Liu MDY & Huang J (2007). Physiological basis for a causal relationship of human obstructive sleep apnoea to hypertension. Exp Physiol 92, 21–26.[Abstract/Free Full Text]
Wolk R & Somers VK (2007). Sleep and the metabolic syndrome. Exp Physiol 92, 67–78.[Abstract/Free Full Text]
Top
Introduction
The review articles