Role of central nervous system nitric oxide in the development of neurogenic pulmonary edema in rats.
OBJECTIVE
The present study was undertaken to evaluate roles of nitric oxide in the central nervous system in the development of neurogenic pulmonary edema. Nitric oxide donor compounds have been reported to be effective for controlling some kinds of pulmonary edema.


METHODS
Randomized trial.


METHODS
Experimental university pharmacology laboratory.


METHODS
Wistar rats anesthetized with pentobarbital.


METHODS
Neurogenic pulmonary edema was induced by injections of fibrinogen and thrombin into the cisterna magna. Physiologic roles of nitric oxide were evaluated by using NG-nitro-l-arginine methyl ester (a nitric oxide synthase inhibitor) or l-arginine (a nitric oxide donor compound). Vagus nerves were either left intact or bilaterally severed 20 mins before the injections of fibrinogen and thrombin.


RESULTS
Because enhanced sympathetic nerve activity mediates neurogenic pulmonary edema, the concentration of neuropeptide Y, a neurotransmitter, in edema fluid was measured by using enzyme-linked immunosorbent assay. To evaluate the severity of pulmonary edema and pulmonary vascular permeability, lung water content and protein concentration in edema fluid were analyzed. In rats with intact vagus nerves, injection of NG-nitro-l-arginine methyl ester into the cisterna magna worsened the pulmonary edema, whereas l-arginine had no effect. In contrast, in vagotomized rats, l-arginine abrogated pulmonary edema, whereas NG-nitro-l-arginine methyl ester exerted no influence. Likewise, the ratio of edema fluid protein to serum protein and the neuropeptide Y concentration were increased by NG-nitro-l-arginine methyl ester in rats with the vagus nerves intact and were diminished by l-arginine in vagotomized rats.


CONCLUSIONS
Neurogenic pulmonary edema is characterized by elevated pulmonary vascular permeability and may be inhibited by nitric oxide production in the medulla oblongata.
Hamdy
O
O
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
Maekawa
H
H
Shimada
Y
Y
Feng
G G
GG
Ishikawa
N
N
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001834:Body Water / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D008526:Medulla Oblongata / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009478:Neuropeptide Y / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014630:Vagus Nerve / Q000601:surgery
D009478:Neuropeptide Y; D011506:Proteins; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester