Nitric oxide in the sinuses of Neandertals

OK, I was reviewing hypotheses about sinus anatomy for a student, and I ran across this one, which I must admit was news to me:

Nitric oxide (NO), a substance produced in the paranasal sinuses, is thought to defend against pathogens among other functions. High levels of NO increase mucuciliary activity. NO levels in both the nasal cavity and the maxillary sinus seem to depend on the size of the paranasal ostia [i.e., the openings of the sinuses into the nasal cavity]: As ostia [sic] size increases, NO levels decrease. It has been hypothesized that the purportedlarge sinuses of Neandertals are a consequence of their need for high NO production to support a vigorous way of life (Rae and Koppe 2004:216).

No, nitric oxide is not laughing gas -- that's nitrous oxide (N2O)! Although for excellent pictures of laughing Neandertals, I highly recommend Kennis and Kennis (whose website, sadly, seems to have disappeared).

Rae and Koppe (2004) draw their account from this meetings abstract by Sam Marquez and colleagues (2002):

The anatomy and function of the Neanderthal upper respiratory tract (URT) has been a topic of great interest, particularly as a possible window on their lifestyles. Neanderthal paranasal sinuses (pns) have been described as expansive although the precise reasons for this are not well understood. However, the pns are the prime site for production of nitric oxide (NO), a gas with neurotransmitter-like functions. In the URT, NO exerts functions on ciliary activity, gland stimulation, and acts as an aerocrine messenger between the upper and lower airways that selectively reverses hypoxic pulmonary vasoconstriction without causing systemic vasodilation. NO also functions in host defense (Fliegelman, Gannon, and Lawson, 1998) insuring sterility of the pns permitting mucus drainage through their ostia into the airflow pathway thus serving as a valuable adjunct in the air-conditioning process of humidification (Gannon et al., 1997).
This qualitative and quantitative study examined pns morphology via CT imaging in a multiregional sample of 125 human skulls and compared them to assessments of the nasal complex in archaic Homo sapiens. Modern groups exhibited population specific pns morphology with respect to ecogeographic localities. Notably, Neanderthal pns dimensions differed from European modern populations. This suggests that Neanderthal pns volumes may reflect a different clade trajectory, perhaps due to differing NO production rate and utilization. We hypothesize that the idiosyncratically large size of Neanderthal pns is related to greater production of NO. This sinonasal / aerocrine adaptation was selected to meet the critical cardiopulmonary system demands imposed by the vigorous lifestyle of Neanderthals (Marquez et al. 2002:107).

Hopefully that research will come out somewhere. The beauty of the sinus production of NO is that it is localized to the respiratory tract. NO metabolism is very important to different systems -- its role as a vasodilator makes it an important regulator of blood pressure, it has a role in the reproductive system, and a role as a neurotransmitter. So it is important for its effects to be localized rather than systemic.

For Neandertals, one could imagine different kinds of balances -- for example, since NO concentration decreases with ostium size, a larger Neandertal ostium might require greater NO productivity to maintain the same function. It doesn't seem too likely that greater productivity was an adaptation to activity level, at least not unless high-activity modern populations were shown to have large sinuses. The Neandertals otherwise are a bit of a contradiction, since in general sinus size seems to decrease with latitude -- apparently a structural side effect of having larger nasal cavities in colder climates. I guess ostium size becomes a pretty crucial parameter to examine, since if large maxillary sinuses were merely a side effect of large faces in Neandertals, the nasal and sinus systems would presumably have evolved to maintain a constant function.

Rae and Koppe (2004) have a good review of other adaptive hypotheses for sinuses. I guess it will take some convincing to get me to think they are specifically adaptive in humans, since their morphology and size is so variable.


Kirihene RKDRA, Rees G, Wormald P-J. 2002. The influence of the size of the maxillary sinus ostium on the nasal and sinus nitric oxide levels. Am J Rhinol 16:261-264. IngentaConnect

Marquez S, Gannon P, Lawson W, Reidenberg J, Laitman J. 2002. Were Neanderthals full of "NO" gas? The relationship between paranasal sinus morphology and nitric oxide production. Am J Phys Anthropol 34(suppl):107.

Rae TC, Koppe T. 2004. Holes in the head: evolutionary interpretations of the paranasal sinuses in catarrhines. Evol Anthropol 13:211-223. DOI link