VOL. 8, No. 1/2, December 2012

D. E. Wardly* [2012] Med. Hypotheses Res. 8: 1-38.

Atrial Natriuretic Peptide: Beyond Natriuresis to an
Understanding of the Clinical Findings in Upper Airway
Resistance Syndrome

Deborah E. Wardly*

7901 Autumn Gate Avenue, Las Vegas, NV 89131, USA

Abstract. This hypothesis paper discusses the “ANP hypothesis” and the scientific
evidence which suggests the following: Atrial Natriuretic Peptide (ANP) levels are markedly
elevated in upper airway resistance syndrome (UARS), more so than in obstructive sleep
apnea syndrome (OSAS), and are responsible for much of the symptomatology in UARS
outside of sleep deprivation. In OSAS ANP resistance develops, as a result of hypoxia as well
as obesity, and this will decrease the somatic and other symptoms that are caused by ANP.
The ANP resistance caused by hypoxia implicates OSAS as a cause of obesity, due to ANP
effect on lipolysis. The effects of ANP on the hypothalamic-pituitary-adrenal axis implicate
UARS as the cause of “adrenal fatigue” and chronic fatigue syndrome (CFS). These effects
may be able to be used to develop a biomarker panel to aid diagnosis and follow up in
UARS. ANP effect on magnesium excretion may explain magnesium deficiency mediated
illnesses which are associated with sleep disordered breathing. Gender differences in ANP
secretion may explain gender differences seen between UARS and OSAS, as well as within the
somatic syndromes. The actions of ANP on Nitric Oxide (NO) suggest the “ANP/NO/ONOO
hypothesis” via upregulation of the NO/ONOO (nitric oxide/peroxynitrite) cycle which has
been implicated in the somatic syndromes. The extreme ANP elevations seen in UARS would
act as a perpetuating factor to maintain the NO/ONOO vicious cycle mechanism and
perpetuate these chronic illnesses once triggered; therefore it is suggested that UARS
underlies all of these chronic somatic syndromes.  

* Correspondence:  Deborah E. Wardly, M.D., 7901 Autumn Gate Avenue, Las Vegas, NV
89131, USA. PHONE: 916-712-0704. FAX: 505-212-1712.