The purpose of this review is to outline the physiological responses associated with the diving response, its functional significance, and its cardiorespiratory control. This review is separated into four major sections. Section one outlines the diving response and its physiology. Section two provides support for the hypothesis that the primary role of the diving response is the conservation of oxygen. The third section describes how the diving response is controlled and provides a model that illustrates the cardiorespiratory interaction. Finally, the fourth section illustrates potential adaptations that result after regular exposure to an asphyxic environment. The cardiovascular and endocrine responses associated with the diving response and apnea are bradycardia, vasoconstriction, and an increase in secretion of suprarenal catecholamines. These responses require the integration of both the cardiovascular system and the respiratory system. The primary role of the diving response is likely to conserve oxygen for sensitive brain and heart tissue and to lengthen the time before the onset of serious hypoxic damage. We suggest that future research should be focused towards understanding the role of altered ventilatory responses in human breath-hold athletes as well as in patients suffering from sleep-disordered breathing.

Abstract-Intermittent hypoxia (IH) is believed to contribute to the pathogenesis of hypertension in obstructive sleep apnea through mechanisms that include activation of the renin-angiotensin system. The objective of this study was to assess the role of the type I angiotensin II receptor in mediating an increase in arterial pressure associated with a single 6-hour IH exposure. Using a double-blind, placebo-controlled, randomized, crossover study design, we exposed 9 healthy male subjects to sham IH, IH with placebo medication, and IH with the type I angiotensin II receptor antagonist losartan. We measured blood pressure, cerebral blood flow, and ventilation at baseline and after exposure to 6 hours of IH. An acute isocapnic hypoxia experimental protocol was conducted immediately before and after exposure to IH. IH with placebo increased resting mean arterial pressure by 7.9Ϯ1.6 mm Hg, but mean arterial pressure did not increase with sham IH (1.9Ϯ1.5 mm Hg) or with losartan IH (Ϫ0.2Ϯ2.4 mm Hg; PϽ0.05). Exposure to IH prevented the diurnal decrease in the cerebral blood flow response to hypoxia, independently of the renin-angiotensin system. Finally, in contrast to other models of IH, the acute hypoxic ventilatory response did not change throughout the protocol. IH increases arterial blood pressure through activation of the type I angiotensin II receptor, without a demonstrable impact on the cerebrovascular or ventilatory response to acute hypoxia. (Hypertension. 2010;56:369-377.)Key Words: blood pressure Ⅲ cerebrovascular circulation Ⅲ hypoxia Ⅲ renin Ⅲ physiology P atients with obstructive sleep apnea (OSA) are exposed to chronic intermittent hypoxia (IH), which is thought to be the underlying mechanism that links OSA with an increased risk of cardiovascular disease. 1 The specific pathophysiologic mechanism whereby OSA causes hypertension has not been fully elucidated, but it has been proposed that persistent sympathoexcitation, oxidative stress, and endothelial dysfunction contribute. 2 Central to this concept is the important interaction between the sympathetic nervous system and the renin-angiotensin system (RAS). Renin release from the kidney is tightly controlled by activity in renal sympathetic nerves. 3 In OSA patients, sympathetic nerve activity, 4 the plasma concentration of angiotensin II (ANG-II), 5 and the vasoconstrictor response to ANG-II are elevated. 6 ANG-II has potent vasoconstrictor capabilities through its action on type I ANG-II receptors (AT 1 Rs) located on vascular smooth muscle cells. 7 ANG-II production can also regulate blood volume by increasing aldosterone production. The combined potential for the RAS to be stimulated by IH and its ability to regulate peripheral resistance and blood volume make it a credible pathway through which OSA can lead to the development of systemic hypertension. The role of the RAS in the IH-dependent increase in arterial blood pressure has yet to be addressed in human experiments.The primary objective of this study was to assess the role of the AT 1 R in ...

Key pointsr The oxygen cost of breathing represents a significant fraction of total oxygen uptake during intense exercise.r At a given ventilation, women have a greater work of breathing compared with men, and because work is linearly related to oxygen uptake we hypothesized that their oxygen cost of breathing would also be greater.r For a given ventilation, women had a greater absolute oxygen cost of breathing, and this represented a greater fraction of total oxygen uptake.r Regardless of sex, those who developed expiratory flow limitation had a greater oxygen cost of breathing at maximal exercise.r The greater oxygen cost of breathing in women indicates that a greater fraction of total oxygen uptake (and possibly cardiac output) is directed to the respiratory muscles, which may influence blood flow distribution during exercise.Abstract We compared the oxygen cost of breathing (V O 2 RM ) in healthy men and women over a wide range of exercise ventilations (V E ). Eighteen subjects (nine women) completed 4 days of testing. First, a step-wise maximal cycle exercise test was completed for the assessment of spontaneous breathing patterns. Next, subjects were familiarized with the voluntary hyperpnoea protocol used to estimateV O 2 RM . During the final two visits, subjects mimicked multiple times (four to six) the breathing patterns associated with five or six different exercise stages. Each trial lasted 5 min, and on-line pressure-volume and flow-volume loops were superimposed on target loops obtained during exercise to replicate the work of breathing accurately. At ß55 l min −1 V E ,V O 2 RM was significantly greater in women. At maximal ventilation, the absoluteV O 2 RM was not different (P > 0.05) between the sexes, but represented a significantly greater fraction of whole-bodyV O 2 in women (13.8 ± 1.5 vs. 9.4 ± 1.1%V O 2 ). During heavy exercise at 92 and 100% V O 2 max , the unit cost ofV E was +0.7 and +1.1 ml O 2 l −1 greater in women (P < 0.05). AtV O 2 max , men and women who developed expiratory flow limitation had a significantly greaterV O 2 RM than those who did not (435 ± 44 vs. 331 ± 30 ml O 2 min −1 ). In conclusion, women have a greateṙ V O 2 RM for a givenV E , and this represents a greater fraction of whole-bodyV O 2 . The greaterV O 2 RM in women may have implications for the integrated physiological response to exercise. Abbreviations EFL, expiratory flow limitation; MEFV, maximal expiratory flow-volume;V E , expired minute ventilation;V Emax , maximal expired minute ventilation;V O2 , oxygen uptake;V O2 max , maximal oxygen uptake;V O2RM , oxygen uptake of the respiratory muscles; WOB, work of breathing.

Chronic intermittent hypoxia increases oxidative stress by increasing production of reactive oxygen species without a compensatory increase in antioxidant activity. This human study shows that reactive oxygen species overproduction modulates increased AHVR. These mechanisms may be responsible for increased AHVR in patients with obstructive sleep apnea.