Endothelin-1 mediates attenuated carotid baroreceptor activity by intermittent hypoxia.
The objectives of the present study were to examine the effects of intermittent hypoxia (IH) on arterial baroreflex function and assess the underlying mechanism(s). Experiments were performed on adult male rats treated with 14 days of IH (15 s of hypoxia, 5 min of normoxia; 8 h/day) or normoxia (control). Arterial blood pressures were elevated in IH-treated rats, and this effect was associated with attenuated heart rate and splanchnic sympathetic nerve responses to arterial baroreflex activation. In IH-treated rats, carotid baroreceptor responses to elevated sinus pressures were attenuated. Endothelin-1 (ET-1) levels were elevated in the carotid sinus region of IH-treated rats, and this effect was associated with increased endothelin converting enzyme (ECE) activity, which generates biologically active ET-1. ET(A) receptor antagonist prevented the effects of IH on carotid baroreceptor activity. In IH-treated rats, reactive oxygen species (ROS) levels were elevated in the carotid sinus region, and antioxidant treatment prevented the effects of IH on ET-1 levels, ECE activity, carotid baroreceptor activity, and baroreflex function. These results demonstrate that 1) IH attenuates arterial baroreflex function, which is in part due to reduced carotid baroreceptor responses to elevated carotid sinus pressure, and 2) IH-induced carotid baroreceptor dysfunction involves reactive oxygen species-dependent upregulation of ET-1 signaling in the carotid sinus region.
Institute for Integrative Physiology and Center for Systems Biology for O(2) Sensing, Biological Sciences Division, University of Chicago, Chicago, Illinois 60637, USA.
Ying-Jie
YJ
Peng
Jayasri
J
Nanduri
Xin
X
Zhang
Ning
N
Wang
Gayatri
G
Raghuraman
Jeanne
J
Seagard
Ganesh K
GK
Kumar
Nanduri R
NR
Prabhakar
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002344:Carotid Body / Q000502:physiology; D002346:Carotid Sinus / Q000502:physiology*; D019332:Endothelin-1 / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D019332:Endothelin-1; D017382:Reactive Oxygen Species