INTRODUCTION Obstructive sleep apnea syndrome (OSA) is a disorder characterized by complete cessations (apneas) and/or par- tial decreases in ventilation (hypopneas) during sleep due to repetitive collapse of the upper airway. Such events are usually accompanied by oxyhemoglobin desaturations, which can be severe. Clinical consequences of OSA are felt to be the result of sleep fragmentation and/or hypox- emia (1–3). Obstructive sleep apnea has been associated with cardiac arrhythmias, hypertension, nighttime confu- sion and neuropsychologic impairment (4–6). Increased mortality and increased risk of death during sleep have also been associated with OSA (7–9). It is now recognized that about 24% of middle age males and 9% of females have apneas during sleep (> 5/hour), and 4% of middle age males and 2% of females have OSA (10). Forty per cent of patients with essential hypertension have OSA and up to 50% of OSA patients have hyperten- sion (11,12). There is now strong evidence from animal experiments and from human epidemiological studies that OSA can cause persistent hypertension both during sleep and during the waking hours (11–14). However, the mechanism for the development or maintenance of hypertension in sleep apnea is not known. Several factors common to the hypertensive and the sleep apneic may be involved, such as obesity and increased sympathetic activity (15–18). In this article, we hypothesize that Obstructive sleep apnea and hypertension: are peripheral chemoreceptors involved? J. S. Loredo, 1 J. L. Clausen, 1 R. A. Nelesen, 2 S. Ancoli-Israel, 2,3 M. G. Ziegler, 1 J. E. Dimsdale 2 1 Department of Medicine, University of California, San Diego, California, USA 2 Department of Psychiatry, University of California, San Diego, California, USA 3 Department of Psychiatry, Veterans Affairs San Diego Healthcare System, San Diego, California, USA Summary The mechanism of pathogenesis of hypertension in patients with obstructive sleep apnea (OSA) is unknown. Many investigators point to the high sympathetic nervous system activity (SNS) observed in OSA patients. However, there is no clear explanation as to the mechanism for the development of SNS hyperactivity in these patients. A common feature of patients with OSA is repetitive bouts of transient hypoxemia during sleep. Repetitive transient hypoxemia in rats has resulted in hypertension. In OSA patients, resolution of nocturnal hypoxemia with CPAP has corrected nocturnal and diurnal hypertension. Also, exposure to hyperoxia reduces blood pressure and sympathetic activity in OSA patients, but not in normals. These data suggest a significant role of peripheral chemoreceptors in the regulation of vascular tone. We hypothesize that peripheral chemoreceptors significantly contribute to the pathogenesis of hypertension in patients with OSA and that this is associated with chemoreceptor hyperactivity. This implies that correcting the intermittent nocturnal hypoxemia alone may prevent the cardiovascular morbidity associated with obstructive sleep apnea. © 2001 Harcourt Publishers Ltd Received 25 May 1999 Accepted 29 November 1999 Correspondence to: Dr José S. Loredo, UCSD Medical Center Department of Medicine, 200 West Arbor Drive, San Diego, CA 92103-8378, USA. Phone: +1 619 543 5740; Fax: +1 619 543 3384; E-mail: jloredo@ucsd.edu 17 Medical Hypotheses (2001) 56(1), 17–19 © 2001 Harcourt Publishers Ltd doi: 10.1054/mehy.2000.1086, available online at http://www.idealibrary.com on This work was supported in part by NIH grants HL44915, AG02711, AG08415, and RR00827.