Molecular Interactions between Gasotransmitters in Patients with Obstructive Sleep Apnea

Patients with obstructive sleep apnea (OSA) have an increased risk of cardiovascular disease (CVD). Nitric oxide (NO) and heme oxygenase-1 (HO-1) affect vascular tone and are vasoprotective. Furthermore, hydrogen sulfide (H2S), an HO-1 inducer, is known to be a major effector molecule driving apneas. This study was conducted to examine the molecular relationships between these gasotransmitters and HO-1 in patients with OSA. Individuals who presented for evaluation for possible OSA were recruited and underwent overnight polysomnography. Individuals with an apnea-hypopnea index (AHI) of >5 per hour (OSA diagnosis) were considered cases (n = 19), while those with an AHI of <5 per hour (n = 6) were the controls. Blood samples were obtained before sleep and again from OSA cases prior to initiating treatment. H2S, NO, and HO-1 levels were assayed. Patients with OSA showed lower NO and H2S levels at baseline compared to controls. NO levels further decreased significantly from baseline in patients at the time of OSA diagnosis, while H2S levels largely showed an increasing trend, which was observed only when the subjects showing a baseline H2S level of >0.5 μM were excluded. Interestingly, analysis of HO-1 did not show a significant change from baseline, confirming the inverse relationship between the two gasotransmitters. The alterations in the bioavailability of endogenous H2S and its molecular interactions with NO and HO-1 regulating vascular tone may play a role in the pathogenesis of CVD in OSA patients.