Abnormally increased nitric oxide synthesis and increased endothelin‐1 in plasma in patients with obstructive sleep apnoea

Abstract

Objective. Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular morbidity and mortality. The mechanism is unknown, but endothelial dysfunction might contribute. We tested the hypothesis that patients with OSA have abnormal nitric oxide (NO) synthesis, which results in an abnormal response in blood pressure, renal hemodynamics, renal tubular function and vasoactive hormones in response to inhibition of the NO synthesis with l‐NMMA. Material and methods. A randomized, placebo‐controlled, single‐blinded, crossover study was done in 13 OSA patients and 14 controls. We measured changes in systolic and diastolic blood pressure (SBP and DBP), pulse rate, glomerular filtration rate, renal plasma flow, fractional excretion of sodium and lithium and plasma concentrations of vasoactive hormones after injection of l‐NMMA and placebo. Results.l‐NMMA induced a significant increase in SBP and DBP in both groups. The placebo‐corrected increase in DBP was more pronounced in patients with OSA than in controls (9 (5–11) versus 3 (1–6) mmHg; p = 0.01). Endothelin‐1 (ET‐1) was significantly higher in patients compared with controls (1.1 (1.0–1.3) versus 0.8 (0.7–0.9) pg/mL; p<0.01). In controls, l‐NMMA induced a small increase in ET‐1, while no changes were seen in patients. The placebo‐corrected change in ET‐1 was lower in patients compared to controls (−01 (−0.3–0.0) versus 0.1 (0.0–0.1) pg/mL; p = 0.04). Conclusions. Patients with OSA have abnormally increased NO synthesis and an increased unresponsive level of ET‐1 in plasma. This might be due to an imbalance between NO synthesis and ET‐1 production.

• Aldosterone
• angiotensin II
• arginine vasopressin
• atrial natriuretic peptide
• blood pressure
• brain natriuretic peptide

Acknowledgements

We thank Lisbeth Mikkelsen, Henriette Vorup Simonsen, Anne‐Mette Ravn Torstensen, Susan Milton Rasmussen and Kirsten Nygaard at the Department of Medical Research and Vera Staghøj at the Section for Pulmonary Diseases, Holstebro Hospital, for skilful technical assistance. The study was supported by grants from the Research Foundation of Ringkøbing County and the Danish Lung Association.