Chronic intermittent hypoxia augments chemoreflex control of sympathetic activity: role of the angiotensin II type 1 receptor.
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 gp91(phox) 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.
Department of Kinesiology, University of Wisconsin, Madison, WI 53706, USA.
Noah J
NJ
Marcus
Yu-Long
YL
Li
Cynthia E
CE
Bird
Harold D
HD
Schultz
Barbara J
BJ
Morgan
D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001049:Apnea / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D013481:Superoxides; D000804:Angiotensin II; D052248:Nitric Oxide Synthase Type I; D019255:NADPH Oxidases; D019808:Losartan