Guest post by Dr. Deborah Wardly.
Recently, my hypothesis paper on Atrial Natriuretic Peptide (ANP) was published, which discusses various actions of ANP and how they might relate to the clinical presentation of OSA and UARS. ANP is known to be elevated in OSA as a result of intrathoracic pressure changes during apneas. This has been noted to be a cause of nocturia in OSA, but there may be other previously unrecognized effects. For example, ANP is very important in lipolysis; the breakdown of fat. But in obesity, there is ANP resistance; meaning that even if there’s lots of ANP around, the body doesn’t see it, so the effect is as if the levels are low. Therefore, ANP resistance might be the key to understanding the obesity in OSA (as well as obesity in general, depending on how prevalent we believe OSA to be); there is evidence that hypoxia may lead ultimately to ANP resistance, suggesting that in OSA, it is the OSA that CAUSES the obesity, and then this becomes a vicious cycle, since we know that obesity makes OSA worse.
Other effects of ANP implicate its possible role in “adrenal fatigue”, due to the fact that ANP suppresses the hypothalamic-pituitary-adrenal axis. In the absence of hypoxia, as in UARS, this would be more prominent and ANP levels and effect should be much higher than in OSA because there would be no ANP resistance. This would also explain why those with UARS are thin, as lipolysis would be activated by the high ANP levels. A hallmark of adrenal insufficiency is orthostatic hypotension, something seen in UARS. ANP would explain the blood pressure differences seen in UARS and OSA: ANP itself lowers blood pressure, explaining lower blood pressures in UARS and then with ANP resistance in conjunction with other factors, the fact that blood pressure rises in OSA. ANP levels go up with exercise, and would explain the exercise intolerance seen in fatiguing illnesses. This theory argues that UARS underlies potentially ALL cases of adrenal fatigue, and possibly most cases of chronic fatigue syndrome. It also argues that the increase in somatic symptoms seen in UARS are mainly due to the actions of ANP.
A high level of ANP doubles the excretion rate of magnesium from the kidney, putting those with sleep disordered breathing at higher risk of magnesium deficiency. Magnesium deficiency from sleep disordered breathing may implicate its involvement in the development of obesity, insulin resistance, atherosclerosis, preeclampsia, hypertension, arrhythmia, inflammation, migraine, and asthma.
There are gender differences in ANP secretion that might explain the gender differences we see between OSA and UARS. For example, testosterone completely eliminates stretch induced release of ANP. Therefore, according to this theory, men with sleep disordered breathing and adequate testosterone levels, would have lower levels of ANP caused by their apneas, and therefore fewer somatic symptoms, compared to women.
There are also polymorphisms of ANP that would lead to much higher levels of ANP in some individuals; might these be the people we see with severe UARS?
As patients with OSA, what has been your experience? Did you have sleep problems only after you gained weight, or did your sleep problems precede your weight gain? If you are a man with UARS, do you have a low testosterone level?