Getting jittery about the mechanism of hypertension in sleep apnoea.

Abstract

Sleep apnoea kills. The prevalence of the sleep-related breathing disorder is high and apparently on the rise. Growing too is the alarming list of associated co-morbidities. What is crystal clear is the causal relationship between sleep apnoea and hypertension. In obstructive sleep apnoea (OSA), recurrent airway obstruction during the night gives rise to repeated bouts of hypoxaemia, with resultant elevated sympathetic nervous activity and pressor responses. The pernicious spillover of heightened sympathetic tone persists during the day when patients do not experience obstructive airway events; thus, sympathetic overactivity is strongly implicated in the manifestation of the daytime hypertensive phenotype in OSA (Hedner et al. 1988). Mechanisms of sympathoexcitation and the subsequent development of hypertension remain elusive. It is established that presympathetic neurones of the rostral ventrolateral medulla show activity entrained to the respiratory cycle. Enhanced respiratory–sympathetic coupling is observed in several animal models of neurogenic hypertension (Moraes et al. 2012, 2014). Importantly, elevated respiratory–sympathetic coupling has been shown to present before the onset of high blood pressure, suggesting a causal influence. Of interest, hyperexcitability in pre- and postinspiratory neurones of the medullary respiratory network has been identified as a key driver of enhanced sympathetic activity in the spontaneously hypertensive rat (Moraes et al. 2014), which is very exciting indeed. Arguing against this potential unifying hypothesis, however, are data that appear to show no increase in the respiratory modulation of sympathetic vasoconstrictor drive in human patients with essential hypertension (Fatouleh & Macefield, 2011). What about OSA? Perturbation in the central control of breathing is a feature of the syndrome. Perhaps enhanced respiratory–sympathetic coupling drives aberrant sympathetic outflow in OSA patients? In this issue of Experimental Physiology, Fatouleh et al. (2014) have the nerve to suggest otherwise! Into the air; and what seemed corporal melted As breath into the wind. Would they had stay'd! So that's that? Not quite: sapere vedere. Time to catch your breath! To explore further the temporal profile of the respiratory modulation of sympathetic nervous output, correlations were constructed allowing a comprehensive analysis of the normalized timing of MSNA activity relative to the respective respiratory cycles for each test subject. This approach revealed a greater respiratory modulation of MSNA in OSA patients, with lower mean MSNA activity during inspiration and expiration, but elevated activity in the postinspiratory phase in comparison to control subjects. In short, whilst the magnitude of the respiratory modulation does not differ between OSA patients and control subjects, a temporal jitter exists such that respiratory–sympathetic coupling is de facto more pronounced in OSA patients. Of note, CPAP treatment had mixed effects on the syncopated respiratory-related rhythm of MSNA in OSA patients (though the authors contend that it was largely reversed by treatment). Of particular interest, CPAP did not completely reverse MSNA levels to control. The relevance of this finding lies in the recognized failure of CPAP to lower blood pressure in OSA patients, including those with confirmed compliant CPAP usage, such as the patients in the study by Fatouleh et al. (2014). And breathe short-winded accents of new broils To be commenced in strands afar remote Those battles lie ahead, but the pressure is rising. We will remain sympathetic to the cause. But should we continue to look for inspiration or simply get to the heart of the matter? Readers are invited to give their opinion on this article. To submit a comment, go to: http://ep.physoc.org/letters/submit/expphysiol;99/10/1283. None declared. None declared.