TY - JOUR
T1 - Chronic intermittent hypoxia augments chemoreflex control of sympathetic activity
T2 - Role of the angiotensin II type 1 receptor
AU - Marcus, Noah J.
AU - Li, Yu Long
AU - Bird, Cynthia E.
AU - Schultz, Harold D.
AU - Morgan, Barbara J.
N1 - Funding Information:
The authors acknowledge the technical assistance of Dr. Safraaz Mahamed, Kristin Sorenson, Scott Smith, and Jenni Ballweg. We are indebted to Drs. E. Burt Olson, Jr. and Steven Polishinski for their assistance with design and operation of the hypoxia chamber. 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 - 2010/4/15
Y1 - 2010/4/15
N2 - Chronic exposure to intermittent hypoxia (CIH) increases carotid sinus nerve activity in normoxia and in response to acute hypoxia. We hypothesized that CIH augments basal and chemoreflex-stimulated sympathetic outflow through an angiotensin receptor-dependent mechanism. Rats were exposed to CIH for 28 days: a subset was treated with losartan. Then, lumbar sympathetic activity was recorded under anesthesia during 20-s apneas, isocapnic hypoxia, and potassium cyanide. We measured carotid body superoxide production and expression of angiotensin II type-1 receptor, neuronal nitric oxide synthase, and NADPH oxidase. Sympathetic activity was higher in CIH vs. control rats at baseline, during apneas and isocapnic hypoxia, but not cyanide. Carotid body superoxide production and expression of angiotensin II type 1 receptor and gp91phox subunit of NADPH oxidase were elevated in CIH rats, whereas expression of neuronal nitric oxide synthase was reduced. None of these differences were evident in animals treated with losartan. CIH-induced augmentation of chemoreflex sensitivity occurs, at least in part, via the renin-angiotensin system.
AB - Chronic exposure to intermittent hypoxia (CIH) increases carotid sinus nerve activity in normoxia and in response to acute hypoxia. We hypothesized that CIH augments basal and chemoreflex-stimulated sympathetic outflow through an angiotensin receptor-dependent mechanism. Rats were exposed to CIH for 28 days: a subset was treated with losartan. Then, lumbar sympathetic activity was recorded under anesthesia during 20-s apneas, isocapnic hypoxia, and potassium cyanide. We measured carotid body superoxide production and expression of angiotensin II type-1 receptor, neuronal nitric oxide synthase, and NADPH oxidase. Sympathetic activity was higher in CIH vs. control rats at baseline, during apneas and isocapnic hypoxia, but not cyanide. Carotid body superoxide production and expression of angiotensin II type 1 receptor and gp91phox subunit of NADPH oxidase were elevated in CIH rats, whereas expression of neuronal nitric oxide synthase was reduced. None of these differences were evident in animals treated with losartan. CIH-induced augmentation of chemoreflex sensitivity occurs, at least in part, via the renin-angiotensin system.
KW - Angiotensin II
KW - Angiotensin antagonist
KW - Chemoreceptors
KW - Oxidative stress
KW - Superoxide
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U2 - 10.1016/j.resp.2010.02.003
DO - 10.1016/j.resp.2010.02.003
M3 - Article
C2 - 20153844
AN - SCOPUS:77949571119
SN - 1569-9048
VL - 171
SP - 36
EP - 45
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
IS - 1
ER -