ME/CFS, POTS - carotid body and gasotransmitters

The hallmark of Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is post exertional malaise (PEM). Research shows that if ME/CFS patients exercise on two consecutive days, they are unable to reproduce their day 1 performance on day 2. VO(2) max is significant lower on day 2. Reference.

The autonomic dysfunction Postural Orthostatic Tachycardia Syndrome (POTS) is a common ME/CFS comorbidity.

Both ME/CFS and POTS may have dysregulation of H(2)S and NO.

I think it is time to take a closer look at the carotid body:

The carotid body is a small cluster of chemoreceptors and supporting cells located near the fork of the carotid artery, which runs along both sides of the throat.

The carotid body functions as a sensor:

• Carotid body monitors the blood’s pH, pCO2, and pO2 and thereby modulates cardiovascular and respiratory function primarily through sympathetic tone. 
• When the carotid body senses acidemia, hypercapnea, or hypoxia, autonomic firing leads to increased blood pressure, heart rate, and respiratory rate.
• The function of the carotid body is complemented by other chemoreceptors, most notably the aortic body located in the aortic arch.

As there are no research in carotid body function in ME/CFS/POTS, we must look elsewhere for information: Role of neurotransmitter gases in the control of the carotid body in heart failure: This review highlights evidence that the alterations in the gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide in the carotid body contribute to the exaggerated carotid body function observed in heart failure. And the paper informs us, that these gas transmitter effects carry important clinical relevance given the importance of the carotid body in the genesis and maintenance of autonomic imbalance and breathing instability in heart failure.

Does alteration in the gasotransmitters in the carotid body contribute to ME/CFS/POTS? Is a possible alteration a result of hypoxia (exercise intolerance)?

Further knowledge here, Hydrogen sulfide as an oxygen sensor:  Cellular H2S production is inversely related to pO2. The author of this paper, Professor of Physiology Kenneth Olson, is to be found at Indiana University, and he emphasises: "Our research has shown that the oxygen sensing mechanism consists of a delicate balance between constitutive production of biologically active H2S in the cell and its oxidation (destruction) by the cell’s mitochondria. Thus the concentration of this important signaling molecule is inversely and inexorably coupled to oxygen availability."

Interesting observation:

It is interesting to notice that Stress peptide PACAP engages multiple signaling pathways within the carotid body to initiate excitatory responses in respiratory and sympathetic chemosensory afferents.

..because the receptor for the stress peptide PACAP has increased expression in ME/CFS patients:

"Compared to healthy individuals, CFS/ME patients displayed significant increases in VPACR2 expression" from this paper Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Update 15. juni 2014: Problems with measurement of H2S: Controversies and Conundrums in Hydrogen Sulfide Biology

Further reading:

VIP and PACAP

Gasotransmitter regulation of ion channels: a key step in O2 sensing by the carotid body
The Carotid Body as a Therapeutic Target for the Treatment of Sympathetically Mediated Diseases