TY - JOUR
T1 - Effect of AT 1 receptor blockade on intermittent hypoxia-induced endothelial dysfunction
AU - Marcus, Noah J.
AU - Philippi, Nathan R.
AU - Bird, Cynthia E.
AU - Li, Yu Long
AU - Schultz, Harold D.
AU - Morgan, Barbara J.
N1 - Funding Information:
This work was supported by grants from the National Heart Lung and Blood Institute [grant numbers HL 074072 to BJM, T32 HL07654 to NJM].
PY - 2012/8/15
Y1 - 2012/8/15
N2 - 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 AT 2R was decreased and the AT 1R:AT 2R 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.
AB - 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 AT 2R was decreased and the AT 1R:AT 2R 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.
KW - Angiotensin II
KW - Endothelial function
KW - Intermittent hypoxia
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U2 - 10.1016/j.resp.2012.05.025
DO - 10.1016/j.resp.2012.05.025
M3 - Article
C2 - 22728949
AN - SCOPUS:84864328415
VL - 183
SP - 67
EP - 74
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
SN - 1569-9048
IS - 2
ER -