Increased nitric oxide synthase activity and expression in the hypothalamus of hindlimb unloaded rats.
Upon return from spaceflight or resumption of normal posture after bed rest, individuals often exhibit cardiovascular deconditioning. Although the mechanisms responsible for cardiovascular deconditioning have yet to be fully elucidated, alterations within the central nervous system have been postulated to be involved. The paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus are important brain regions in control of sympathetic outflow and body fluid homeostasis. Nitric oxide (NO) modulates the activity of PVN and SON neurons, and alterations in NO transmission within these brain regions may contribute to symptoms of cardiovascular deconditioning. The purpose of the present study was to examine nitric oxide synthase (NOS) activity and expression in the PVN and SON of control and hindlimb unloaded (HU) rats, an animal model of cardiovascular deconditioning. The number of neurons exhibiting NOS activity as assessed by NADPH-diaphorase staining was significantly greater in the PVN but not SON of HU rats. Western blot analysis revealed that neuronal NOS (nNOS) but not endothelial NOS (eNOS) protein expression was higher in the PVN of HU rats. In the SON, there was a strong trend for an increase in nNOS (p=0.052) and a significant increase in eNOS expression in HU rats. Our results suggest that increased nNOS in the PVN contributes to autonomic and humoral alterations following cardiovascular deconditioning. In contrast, the functional significance of increases in nNOS and eNOS protein in the SON may be related to alterations in vasopressin release observed previously in HU rats.
Mueller
Patrick J
PJ
Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211-3300, USA. MuellerP@missouri.edu
Foley
C Michael
CM
Heesch
Cheryl M
CM
Cunningham
J Thomas
JT
Zheng
Hong
H
Patel
Kaushik P
KP
Hasser
Eileen M
EM
D000818:Animals; D018493:Cardiovascular Deconditioning / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D004195:Disease Models, Animal; D019417:Hindlimb Suspension / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000201:enzymology*; D013564:Sympathetic Nervous System / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology; D014893:Weightlessness / Q000009:adverse effects*; D018474:Weightlessness Simulation / Q000379:methods
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009252:NADPH Dehydrogenase