OBJECTIVES: Intermittent periods of hypoxemia such as during periodic breathing are associated with hypertension and increased sympathetic activity. In patients with sleep apnea syndrome, hypertension is common. Treating apnea improves hypertension and reduces sympathetic outflow. The aim of the present study was to investigate the phenomenon and mechanisms of spontaneous periodic breathing in patients with hypertension. METHOD: We examined 43 hypertensive patients with untreated hypertension without left-ventricular dysfunction, heart failure or sleep apnea syndrome. Muscle sympathetic nerve activity (MSA), heart rate (HR), blood pressure (BP) and respiration were continuously recorded at rest and during cold-pressor testing. Oxygen and a CO2-enriched gas were used to test central and peripheral chemoreceptors, respectively. Baroreceptor gain was measured using the alpha method. RESULTS: Seven out of 43 patients showed spontaneous periodic breathing while awake. No difference in MSA, HR and BP was seen between patients with and without periodic breathing at rest except the breathing pattern. However, the cold-pressor test caused a larger increase of MSA in patients with periodic breathing (203 +/- 62 vs. 62 +/- 8%, P < 0.0001 by ANOVA), as well as systolic (46 +/- 6 vs. 25 +/- 3 mmHg, P = 0.002) and diastolic BP (26 +/- 5 vs. 12 +/- 1 mmHg, P = 0.004, ANOVA). Baroreceptor gain was markedly higher in patients with periodic breathing. Chemoreceptor sensitivity was comparable. CONCLUSION: Spontaneous periodic breathing is relatively common in patients with hypertension and is associated with greatly enhanced responses to cold-pressor testing. We suggest increased baroreceptor gain and sympathetic outflow as a cause for the oscillatory respiration pattern via barorespiratory coupling.