Intermittent Hypoxia Leads to Endothelin-Dependent Hypertension in a Rat Model of Sleep Apnea.
Clinical studies of sleep apnea demonstrate that the associated hypoxia/hypercapnia (IH) causes systemic hypertension. Additional studies have found that patients with sleep apnea have elevated plasma levels of endothelin. We hypothesized that IH causes sustained hypertension by increasing endothelin production. Three days after surgery to implant arterial and venous catheters, rats were placed in chambers flushed with room air for 90 secs (21% O2/0% CO2) followed by 90 secs hypoxic/hypercapnic air (5% O2/5% CO2). This cycle was repeated throughout an 8 hr daily exposure period. Mean arterial pressure (MAP) was measured daily before the start of IH exposure. After 12 days of IH when MAP was significantly elevated (day 1=105±4 mmHg, day 12=140±7 mmHg), cumulative doses of a non-selective ET-receptor antagonist (PD145065) was administered iv to rats in room air. PD145065 caused a concentration-dependent decrease in MAP in IH rats but did not alter blood pressure in non-IH control rats. We conclude that increased endothelin synthesis during IH causes hypertension.