Role of endothelin in intermittent hypoxia-induced hypertension

Clinical studies suggest that sleep apnea causes systemic hypertension. In addition, patients with sleep apnea have elevated plasma levels of endothel in-1 (ET-1). We hypothesized that the intermittent hypoxia/hypercapnia (IH) associated with sleep apnea causes hypertension by increasing ET-1 product ion. To test this hypothesis, rats with arterial and venous catheters were placed in Plexiglas chambers. IH rat chambers were flushed with an N-2-CO2 mixture for 90 seconds to achieve hypoxia/hypercapnia (5% O-2-5% CO2) follo wed by 90 seconds of compressed air to achieve normoxia (21% O-2-0% CO2). C ontrol rat chambers were flushed with 90 seconds of air-air cycles. Cycles for both groups were repeated 8 hours per day for 11 days. Resting mean art erial pressure (MAP) and heart rate were recorded daily before the start of exposure. After 11 days, MAP was significantly elevated in IH rats compare d with initial MAP (109+/-5 mm Hg initial, 139+/-11 mm Hg day 11) and compa red with air-air rats (110+/-4 mm Hg). On day 11, cumulative doses of PD145 065 (a nonselective ET-receptor antagonist) were administered intravenously to the rats breathing room air. PD145065 caused a dose-dependent decrease in MAP in IH rats but did not alter MAP in air-air rats. Plasma ET-1 measur ed by radioimmunoassay was significantly increased on days 5 and 11 in the IH rats compared with day 1 and compared with air-air rats. There was no si gnificant change in plasma ET-1 over time in air-air rats. We conclude that IH exposure increases both MAP and plasma ET-1 and that the increased ET-1 may contribute to the hypertension.