Effect of AT1 receptor blockade on intermittent hypoxia-induced endothelial dysfunction

Chronic intermittent hypoxia (CIH) raises arterial pressure, impairs vasodilator responsiveness, and increases circulating angiotensin II (Ang II); however, the role of Ang II in CIH-induced vascular dysfunction is unknown. Rats were exposed to CIH or room air (NORM), and a subset of these animals was treated with losartan (Los) during the exposure period. After 28 days, vasodilatory responses to acetylcholine or nitroprusside were measured in isolated gracilis arteries. Superoxide levels and Ang II receptor protein expression were measured in saphenous arteries. After 28 days, arterial pressure was increased and acetylcholine-induced vasodilation was blunted in CIH vs. NORM, and this was prevented by Los. Responses to nitroprusside and superoxide levels did not differ between CIH and NORM. Expression of AT2R was decreased and the AT1R:AT2R ratio was increased in CIH vs. NORM, but this was unaffected by Los. These results indicate that the blood pressure elevation and endothelial dysfunction associated with CIH is dependent, at least in part, on RAS signaling.

► CIH increases arterial pressure and causes vascular endothelial dysfunction.
► Blockade of the angiotensin II type I receptor with losartan prevents increases in arterial pressure and endothelial dysfunction associated with CIH.
► CIH was not associated with increased superoxide levels in saphenous arteries.
► The AT1/AT2 receptor ratio in saphenous arteries was increased by CIH but unaffected by losartan.