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 oxi de 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, Design: Randomized trial. Setting: Experimental university pharmacology laboratory. Subjects: Wistar rats anesthetized with pentobarbital, Interventions: Neurogenic pulmonary edema was induced by injections of fibr inogen and thrombin into the cisterna magna. Physiologic roles of nitric ox ide were evaluated by using N-G-nitro-L-arginine methyl ester (a nitric oxi de synthase inhibitor) or L-arginine (a nitric oxide donor compound), Vagus nerves were either left intact or bilaterally severed 20 mins before the i njections of fibrinogen and thrombin. Measurements and Main 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 immun osorbent as-say. To evaluate the severity of pulmonary edema and pulmonary vascular permeability, lung water content and protein concentration in edem a fluid were analyzed. In rats with intact vagus nerves, injection of N-G-n itro-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 N-G-nitro-L-arginine methyl ester exerted no influence, Likewise, the ratio of edema fluid protein to s erum protein and the neuropeptide Y concentration were increased by N-G-nit ro-L-arginine methyl ester in rats with the vagus nerves intact and were di minished by L-arginine in vagotomized rats. Conclusions: Neurogenic pulmonary edema is characterized by elevated pulmon ary vascular permeability and may be inhibited by nitric oxide production i n the medulla oblongata.