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This issue of the Journal of Applied Physiology introduces a new Highlighted Topics series, "Physiological and Genomic Consequences of Intermittent Hypoxia." The physiological responses to acute and chronic (continuous) hypoxia have been the focus of numerous studies that have produced valuable insight into the cellular and molecular mechanisms underlying the integrative responses and adaptations to hypoxia. However, in clinical settings, many hypoxic episodes are not continuous but rather intermittent in nature, often occurring over prolonged periods of time. One example of intermittent hypoxia involves the repetitive apnea/hypopnea events associated with obstructive sleep apnea in adults and children. Other instances in which intermittent hypoxia occurs include the apnea of prematurity in infants and congenital hypoventilation syndrome, as well as the episodes of hypoxia that occur in a variety of respiratory and cardiovascular diseases. Yet another example is sickle cell anemia, in which intermittent hypoxia and ischemia are characteristic of sickle cell crises.

The incidence of intermittent hypoxia is not trivial, as it affects a large proportion of the population. For example, in the United States, more than 15 million people suffer from obstructive sleep apnea; this includes approximately 24% of men, 9% of women, and 2% of children. The incidence of apnea is also very high in premature babies, with nearly all infants below 30 wk of gestation experiencing apnea. Although deliveries below 30 wk of gestation represent only a small percentage of all deliveries in the United States, the probability of survival for these infants has dramatically increased, making the study of the developmental consequences of intermittent hypoxia even more important as an area of investigation.

The potential health-related consequences associated with intermittent hypoxia are numerous, affecting nearly every organ system from cardiovascular to neurological. The causal linkage of intermittent hypoxia with physiological and pathophysiological adaptations is not well understood and is clearly an area of research that needs to be emphasized. By choosing this topic for the Highlighted Topics series, the Associate Editors and I hope to stimulate thoughts in this important area of research by reviewing some of what is known and what is unknown about the cellular and molecular responses to intermittent hypoxia.

The first issue of the intermittent hypoxia series features two mini-reviews that focus on some of the physiological and pathophysiological adaptations to hypoxia at the integrative level. In the first mini-review, "Intermittent hypoxia: physiological and pathophysiological responses," Dr. Judith Neubauer focuses on the dichotomy between the use of intermittent hypoxia as a training technique to produce physiological adaptations consistent with improved exercise performance vs. the pathophysiological consequences of intermittent hypoxia associated with obstructive sleep apnea. Future studies will be necessary to determine causality and the cellular and molecular mechanisms of these adaptations as well as the thresholds for eliciting protective vs. deleterious responses and their ability to be reversed. One of the pathophysiological consequences of intermittent hypoxia, persistent hypertension, has begun to be studied in this manner. In the second mini-review, "Physiological consequences of intermittent hypoxia: systemic blood pressure," Dr. Eugene Fletcher focuses on a model of intermittent hypoxia that causes a sustained increase in blood pressure in rats due to a hypoxia-induced adaptation of sympathetic nerve activity. The peripheral and central sites that are involved in this adaptation of sympathetic output and the specific cellular and molecular mechanisms of these adaptive processes are questions that will require further exploration.

Adaptations to intermittent hypoxia undoubtedly involve a direct effect of intermittent hypoxia on genes and cellular processes. In this regard, fertile areas of study would include the genes and cellular processes involved in transducing the intermittent hypoxia stimulus, the cell signaling cascade that is involved in modifying the cellular response, and the interactions of these responses with other conditions of plasticity (e.g., early development and aging). In the second issue of this series, two mini-reviews will focus on the effect of intermittent hypoxia at the molecular and cellular level in both the adult and neonatal animals. In the first mini-review, "Carotid body oxygen sensing during intermittent hypoxia: cellular and genetic mechanisms," Dr. Nanduri Prabhakar highlights the impact of intermittent hypoxia on oxygen-sensing mechanisms at the carotid body chemoreceptors and discusses potential cellular and genetic mechanisms that contribute to intermittent hypoxia-induced alterations in carotid body function. In the second mini-review, "Intermittent hypoxia during development: critical windows of vulnerability and plasticity," Drs. David Gozal and Evelyne Gozal explore why intermittent hypoxia may induce genomic, proteomic, and phenotypic alterations that tend to be more pronounced and more prolonged in developing animals compared with adults. The results of such exploration may lead to the formulation of intervention strategies that would reduce the overall vulnerability of the infant or young child to apnea and sudden death.

In the third issue of this series, two final mini-reviews will focus on how repeated episodes of hypoxia cause changes in systems as diverse as neuronal excitability and muscle metabolism and mechanics. The plasticity of these systems results in adaptations that alter the neural reflexes of motor control as well as the mechanical characteristics of most muscle types. In the first mini-review, "Intermittent hypoxia and respiratory plasticity," Dr. Gordon S. Mitchell and colleagues consider the unique influence of episodic hypoxia on respiratory motor control. They focus on respiratory plasticity in normal adults but also explore the differential manifestations of intermittent hypoxia on respiration during development and old age. The second mini-review, "Adaptive responses of skeletal and cardiac muscle to intermittent hypoxia," by Drs. Thomas L. Clanton and Paul Klawitter, provides insight into the pathological and physiological influence of intermittent hypoxia on skeletal muscle. Such information may be important in devising strategies to improve exercise performance or in obviating maladaptations of skeletal muscle.

The high incidences of intermittent hypoxia and obstructive sleep apnea, chronic obstructive pulmonary disease, heart failure, and other conditions emphasize the need for additional information regarding the cellular and molecular adaptations that are induced. As with previous Highlighted Topics series, the Associate Editors and I hope that this series will stimulate further research in the area of intermittent hypoxia under both normal and pathophysiological conditions. Certainly, many questions remain unanswered in this area of investigation, but the introduction of cellular and molecular techniques should provide new insight into basic mechanisms for adaptive and maladaptive responses to intermittent hypoxia.