Intermittent Hypoxia Increases Arterial Blood Pressure in Humans Through a Renin-Angiotensin System–Dependent Mechanism

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 56; no. 3; pp. 369 - 377
• Main Authors: Foster, Glen E., Hanly, Patrick J., Ahmed, Sofia B., Beaudin, Andrew E., Pialoux, Vincent, Poulin, Marc J.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.09.2010; Lippincott Williams & Wilkins; American Heart Association
• Subjects: Adult; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers - pharmacology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiology. Vascular system; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Cross-Over Studies; Double-Blind Method; Endocrine kidney. Renin-angiotensin-aldosterone system; Fundamental and applied biological sciences. Psychology; Humans; Hypoxia - physiopathology; Life Sciences; Losartan - pharmacology; Male; Medical sciences; Receptor, Angiotensin, Type 1 - physiology; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Vertebrates: endocrinology; Human; Hypertension; Oxygen; Renin angiotensin system; cerebrovascular circulation; Intermittent; renin; physiology; Hypoxia; Cardiovascular disease; Arterial pressure; Blood pressure
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.110.152108

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 7.9±1.6 mm Hg, but mean arterial pressure did not increase with sham IH (1.9±1.5 mm Hg) or with losartan IH (−0.2±2.4 mm Hg; P<0.05). 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.