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

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.

Increased nocturnal sodium excretion in obstructive sleep apnoea. Relation to nocturnal change in diastolic blood pressure.

OBJECTIVE: The mechanisms involved in the development and maintenance of hypertension in obstructive sleep apnoea (OSA) are not clear. We hypothesized that OSA patients have an abnormal renal handling of sodium and water during the night. MATERIAL AND METHODS: We studied 29 OSA patients and 19 healthy controls at night with serial determinations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), arginine vasopressin (AVP), aldosterone (Aldo), fractional urinary excretion of sodium (FE(Na)), free water clearance (C(H2O)), urinary excretion of aquaporin 2 (u-AQP2), systolic blood pressure (SBP), diastolic blood pressure (DBP) and oxygen saturation. RESULTS: OSA patients had a higher FE(Na) (0.6 (0.4-1.0) versus 0.4 (0.3-0.6) %; p = 0.017), SBP (129 (114-145) versus 114 (106-122) mmHg; p = 0.001) and DBP (81 (72-87) versus 71 (65-74) mmHg; p<0.001) than healthy controls at night. In hypertensive OSA patients, the FE(Na) correlated significantly with the change in nocturnal DBP (r (2) = 0.411; p = 0.010). Mean level of AVP during the night was higher in OSA patients compared with healthy controls (1.1 (0.8-1.4) versus 0.8 (0.6-1.1) pmol/L; p = 0.033) and correlated with SBP. ANP, BNP, Aldo, C(H2O) and u-AQP2 were the same in OSA and controls. CONCLUSIONS: We conclude that the higher fractional excretion of sodium in OSA is most likely attributable to pressure natriuresis. The correlation between mean AVP and blood pressure suggests that AVP may be part of the pathogenetic mechanism underlying hypertension in these patients.