Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea

Chemoreflex sensitization produced by chronic intermittent hypoxia (CIH) in rats is attenuated by angiotensin II type 1 receptor (AT1R) blockade. AT1R blockade and xanthine oxidase inhibition both ameliorate CIH-induced endothelial dysfunction. We hypothesized treatment with losartan and allopurinol would reduce chemoreflex sensitivity and improve hypoxic vasodilation in patients with obstructive sleep apnoea (OSA). Eighty-six hypertensive patients with apnoea-hypopnoea index ≥25 events/hr and no other cardiovascular, pulmonary, renal, or metabolic disease were randomly assigned to receive allopurinol, losartan, or placebo for 6 weeks. Treatment with other medications and/or continuous positive airway pressure (CPAP) remained unchanged. Tests of chemoreflex sensitivity and hypoxic vasodilation were performed during wakefulness before and after treatment. Ventilation (pneumotachography), muscle sympathetic nerve activity (microneurography), heart rate (electrocardiography), arterial oxygen saturation (pulse oximetry), blood pressure (sphygmomanometry), forearm blood flow (venous occlusion plethysmography), and cerebral flow velocity (transcranial Doppler ultrasound) were measured during eupneic breathing and graded reductions in inspired O2 tension. Losartan and allopurinol lowered arterial pressure measured during eupneic breathing and exposure to acute hypoxia. Neither drug altered the slopes of ventilatory, sympathetic, or cardiovascular responses to acute hypoxia. We conclude that losartan and allopurinol are viable pharmacotherapeutic adjuncts for achieving blood pressure control in hypertensive OSA patients, even those who are adequately treated with CPAP.